chr2-85667185-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000542.5(SFTPB):​c.196-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,606,802 control chromosomes in the GnomAD database, including 106,754 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8087 hom., cov: 32)
Exomes 𝑓: 0.36 ( 98667 hom. )

Consequence

SFTPB
NM_000542.5 splice_region, intron

Scores

2
Splicing: ADA: 0.009874
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.39
Variant links:
Genes affected
SFTPB (HGNC:10801): (surfactant protein B) This gene encodes the pulmonary-associated surfactant protein B (SPB), an amphipathic surfactant protein essential for lung function and homeostasis after birth. Pulmonary surfactant is a surface-active lipoprotein complex composed of 90% lipids and 10% proteins which include plasma proteins and apolipoproteins SPA, SPB, SPC and SPD. The surfactant is secreted by the alveolar cells of the lung and maintains the stability of pulmonary tissue by reducing the surface tension of fluids that coat the lung. The SPB enhances the rate of spreading and increases the stability of surfactant monolayers in vitro. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 1, also called pulmonary alveolar proteinosis due to surfactant protein B deficiency, and are associated with fatal respiratory distress in the neonatal period. Alternatively spliced transcript variants encoding the same protein have been identified.[provided by RefSeq, Feb 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 2-85667185-G-T is Benign according to our data. Variant chr2-85667185-G-T is described in ClinVar as [Benign]. Clinvar id is 165206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85667185-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SFTPBNM_000542.5 linkc.196-8C>A splice_region_variant, intron_variant Intron 2 of 10 ENST00000519937.7 NP_000533.4 P07988D6W5L6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SFTPBENST00000519937.7 linkc.196-8C>A splice_region_variant, intron_variant Intron 2 of 10 1 NM_000542.5 ENSP00000428719.2 P07988

Frequencies

GnomAD3 genomes
AF:
0.301
AC:
45785
AN:
151932
Hom.:
8087
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.105
Gnomad AMI
AF:
0.455
Gnomad AMR
AF:
0.372
Gnomad ASJ
AF:
0.480
Gnomad EAS
AF:
0.375
Gnomad SAS
AF:
0.410
Gnomad FIN
AF:
0.327
Gnomad MID
AF:
0.462
Gnomad NFE
AF:
0.375
Gnomad OTH
AF:
0.341
GnomAD2 exomes
AF:
0.361
AC:
90187
AN:
249836
AF XY:
0.367
show subpopulations
Gnomad AFR exome
AF:
0.0919
Gnomad AMR exome
AF:
0.400
Gnomad ASJ exome
AF:
0.479
Gnomad EAS exome
AF:
0.379
Gnomad FIN exome
AF:
0.322
Gnomad NFE exome
AF:
0.370
Gnomad OTH exome
AF:
0.376
GnomAD4 exome
AF:
0.363
AC:
528395
AN:
1454752
Hom.:
98667
Cov.:
33
AF XY:
0.366
AC XY:
265263
AN XY:
723956
show subpopulations
African (AFR)
AF:
0.0914
AC:
3055
AN:
33436
American (AMR)
AF:
0.405
AC:
18029
AN:
44544
Ashkenazi Jewish (ASJ)
AF:
0.482
AC:
12559
AN:
26076
East Asian (EAS)
AF:
0.379
AC:
15012
AN:
39616
South Asian (SAS)
AF:
0.402
AC:
34586
AN:
86010
European-Finnish (FIN)
AF:
0.317
AC:
16930
AN:
53342
Middle Eastern (MID)
AF:
0.415
AC:
2380
AN:
5738
European-Non Finnish (NFE)
AF:
0.366
AC:
404426
AN:
1105822
Other (OTH)
AF:
0.356
AC:
21418
AN:
60168
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.445
Heterozygous variant carriers
0
14804
29607
44411
59214
74018
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
12730
25460
38190
50920
63650
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.301
AC:
45789
AN:
152050
Hom.:
8087
Cov.:
32
AF XY:
0.301
AC XY:
22406
AN XY:
74320
show subpopulations
African (AFR)
AF:
0.105
AC:
4345
AN:
41502
American (AMR)
AF:
0.372
AC:
5682
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.480
AC:
1666
AN:
3472
East Asian (EAS)
AF:
0.376
AC:
1939
AN:
5158
South Asian (SAS)
AF:
0.410
AC:
1976
AN:
4814
European-Finnish (FIN)
AF:
0.327
AC:
3462
AN:
10592
Middle Eastern (MID)
AF:
0.463
AC:
136
AN:
294
European-Non Finnish (NFE)
AF:
0.375
AC:
25449
AN:
67926
Other (OTH)
AF:
0.342
AC:
720
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1566
3131
4697
6262
7828
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
466
932
1398
1864
2330
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.343
Hom.:
8473
Bravo
AF:
0.296
Asia WGS
AF:
0.370
AC:
1285
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Nov 12, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

not specified Benign:2
Feb 21, 2013
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

232-8C>A in intron 3 of SFTPB: This variant is not expected to have clinical sig nificance because it has been identified in 37.5% (3227/8600) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs3024798). -

-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Surfactant metabolism dysfunction, pulmonary, 1 Benign:2
Jul 15, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary pulmonary alveolar proteinosis Benign:1
Oct 26, 2015
Ambry Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
10
DANN
Benign
0.82
PhyloP100
1.4
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0099
dbscSNV1_RF
Benign
0.092
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3024798; hg19: chr2-85894308; COSMIC: COSV60893037; COSMIC: COSV60893037; API