chr10-79611973-C-G

Variant names:

Variant summary

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

The NM_005411.5(SFTPA1):c.148C>G(p.Leu50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,322,774 control chromosomes in the GnomAD database, including 258,923 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20962 hom., cov: 29)

Exomes 𝑓: 0.57 ( 237961 hom. )

Consequence

SFTPA1
NM_005411.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.893

Publications

39 publications found

Variant links:

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

SFTPA1 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 (MetaRNN=2.2757053E-4).

BP6

Variant 10-79611973-C-G is Benign according to our data. Variant chr10-79611973-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 227062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5 link	c.148C>G	p.Leu50Val	missense_variant	Exon 3 of 6	ENST00000398636.8	NP_005402.3	Q8IWL2-1A0A024QZP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8 link	c.148C>G	p.Leu50Val	missense_variant	Exon 3 of 6	1	NM_005411.5	ENSP00000381633.3		Q8IWL2-1

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

78464

AN:

150688

Hom.:

20968

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.737

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.480

GnomAD2 exomes

AF:

0.494

AC:

117251

AN:

237278

AF XY:

0.492

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.563

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.503

GnomAD4 exome

AF:

0.573

AC:

671034

AN:

1171968

Hom.:

237961

Cov.:

AF XY:

0.565

AC XY:

333686

AN XY:

591048

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.450

AC:

12439

AN:

27670

American (AMR)

AF:

0.439

AC:

19005

AN:

43320

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

10325

AN:

24088

East Asian (EAS)

AF:

0.304

AC:

11214

AN:

36890

South Asian (SAS)

AF:

0.363

AC:

29027

AN:

79926

European-Finnish (FIN)

AF:

0.562

AC:

28885

AN:

51354

Middle Eastern (MID)

AF:

0.342

AC:

1742

AN:

5088

European-Non Finnish (NFE)

AF:

0.623

AC:

531464

AN:

852770

Other (OTH)

AF:

0.530

AC:

26933

AN:

50862

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.370

Heterozygous variant carriers

10830

21661

32491

43322

54152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.520

AC:

78474

AN:

150806

Hom.:

20962

Cov.:

AF XY:

0.512

AC XY:

37708

AN XY:

73612

show subpopulations

African (AFR)

AF:

0.470

AC:

19316

AN:

41112

American (AMR)

AF:

0.466

AC:

7087

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1524

AN:

3454

East Asian (EAS)

AF:

0.290

AC:

1465

AN:

5048

South Asian (SAS)

AF:

0.354

AC:

1682

AN:

4752

European-Finnish (FIN)

AF:

0.575

AC:

6025

AN:

10472

Middle Eastern (MID)

AF:

0.432

AC:

126

AN:

292

European-Non Finnish (NFE)

AF:

0.587

AC:

39593

AN:

67496

Other (OTH)

AF:

0.475

AC:

990

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

1713

3427

5140

6854

8567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.518

Hom.:

3611

Bravo

AF:

0.515

ExAC

AF:

0.496

AC:

60242

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 13680361) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 12, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Leu65Val in exon 3 of SFTPA1: This variant is not expected to have clinical si gnificance it has been identified in 57% (36928/65022) of European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1136450). -

SFTPA1-related disorder

Benign:1

May 24, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.040

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.047

T;T;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.17

.;T;T;.;T

MetaRNN

Benign

0.00023

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.60

N;N;.;.;.

PhyloP100

-0.89

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.58

N;N;N;N;N

REVEL

Benign

0.021

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.73

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.069

MPC

0.017

ClinPred

0.0099

GERP RS

-3.0

Varity_R

0.036

gMVP

0.096

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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chr10-79611973-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over