chr2-85667185-G-T

Position:

chr2-85667185-G-T

Variant summary

Our verdict is Benign. Variant got -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

Splicing: ADA: 0.009874

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]

SFTPB links:

SFTPB (HGNC:):

SFTPB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SFTPB	NM_000542.5 linkuse as main transcript	c.196-8C>A		splice_region_variant, intron_variant		ENST00000519937.7	NP_000533.4	P07988D6W5L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPB	ENST00000519937.7 linkuse as main transcript	c.196-8C>A		splice_region_variant, intron_variant		1	NM_000542.5	ENSP00000428719.2		P07988

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45785

AN:

151932

Hom.:

8087

Cov.:

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

GnomAD3 exomes

AF:

0.361

AC:

90187

AN:

249836

Hom.:

17128

AF XY:

0.367

AC XY:

49581

AN XY:

135002

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 SAS exome

AF:

0.402

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.:

AF XY:

0.366

AC XY:

265263

AN XY:

723956

show subpopulations

Gnomad4 AFR exome

AF:

0.0914

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.379

Gnomad4 SAS exome

AF:

0.402

Gnomad4 FIN exome

AF:

0.317

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.301

AC:

45789

AN:

152050

Hom.:

8087

Cov.:

AF XY:

0.301

AC XY:

22406

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.480

Gnomad4 EAS

AF:

0.376

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.375

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.329

Hom.:

4970

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Surfactant metabolism dysfunction, pulmonary, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2015

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

DANN

Benign

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over