2-85667185-G-T

Variant names:

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

Splicing: ADA: 0.009874

Clinical Significance

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

Conservation

PhyloP100: 1.39

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

surfactant metabolism dysfunction, pulmonary, 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

SFTPB links:

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 VariationId is 165206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000542.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPB	NM_000542.5	MANE Select	c.196-8C>A	splice_region intron	N/A	NP_000533.4
SFTPB	NM_198843.3		c.196-8C>A	splice_region intron	N/A	NP_942140.3	P07988
SFTPB	NM_001367281.1		c.196-8C>A	splice_region intron	N/A	NP_001354210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SFTPB	ENST00000519937.7	TSL:1 MANE Select	c.196-8C>A	splice_region intron	N/A	ENSP00000428719.2	P07988
SFTPB	ENST00000393822.7	TSL:1	c.196-8C>A	splice_region intron	N/A	ENSP00000377409.4	P07988
SFTPB	ENST00000409383.7	TSL:1	c.196-8C>A	splice_region intron	N/A	ENSP00000386346.2

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

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.:

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

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

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.:

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

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

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Surfactant metabolism dysfunction, pulmonary, 1 (2)

Hereditary pulmonary alveolar proteinosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over