rs2243639

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_003019.5(SFTPD):c.538A>G(p.Thr180Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,605,800 control chromosomes in the GnomAD database, including 325,312 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39961 hom., cov: 32)

Exomes 𝑓: 0.62 ( 285351 hom. )

Consequence

SFTPD
NM_003019.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.00

Publications

87 publications found

Variant links:

Genes affected

SFTPD (HGNC:10803): (surfactant protein D) The protein encoded by this gene is part of the innate immune response, protecting the lungs against inhaled microorganisms and chemicals. The encoded protein may also be involved in surfactant metabolism. [provided by RefSeq, Jul 2015]

SFTPD links:

ENSG00000283913 (HGNC:):

ENSG00000283913 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=2.466303E-6).

BP6

Variant 10-79941966-T-C is Benign according to our data. Variant chr10-79941966-T-C is described in ClinVar as [Benign]. Clinvar id is 165215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5 link	c.538A>G	p.Thr180Ala	missense_variant	Exon 5 of 8	ENST00000372292.8	NP_003010.4	P35247
SFTPD	XM_011540087.2 link	c.538A>G	p.Thr180Ala	missense_variant	Exon 5 of 8		XP_011538389.1	P35247
SFTPD	XM_011540088.3 link	c.421A>G	p.Thr141Ala	missense_variant	Exon 4 of 7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8 link	c.538A>G	p.Thr180Ala	missense_variant	Exon 5 of 8	1	NM_003019.5	ENSP00000361366.3		P35247

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107888

AN:

151984

Hom.:

39889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.696

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.790

Gnomad SAS

AF:

0.739

Gnomad FIN

AF:

0.596

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.693

GnomAD2 exomes

AF:

0.657

AC:

164431

AN:

250320

AF XY:

0.655

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.809

Gnomad FIN exome

AF:

0.605

Gnomad NFE exome

AF:

0.601

Gnomad OTH exome

AF:

0.641

GnomAD4 exome

AF:

0.623

AC:

905035

AN:

1453698

Hom.:

285351

Cov.:

AF XY:

0.625

AC XY:

452022

AN XY:

723626

show subpopulations

African (AFR)

AF:

0.942

AC:

31354

AN:

33294

American (AMR)

AF:

0.616

AC:

27513

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

16634

AN:

26074

East Asian (EAS)

AF:

0.758

AC:

30075

AN:

39652

South Asian (SAS)

AF:

0.726

AC:

62479

AN:

86062

European-Finnish (FIN)

AF:

0.608

AC:

32436

AN:

53310

Middle Eastern (MID)

AF:

0.668

AC:

3765

AN:

5636

European-Non Finnish (NFE)

AF:

0.599

AC:

661506

AN:

1104936

Other (OTH)

AF:

0.654

AC:

39273

AN:

60050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

15735

31470

47206

62941

78676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.710

AC:

108028

AN:

152102

Hom.:

39961

Cov.:

AF XY:

0.711

AC XY:

52826

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.928

AC:

38542

AN:

41534

American (AMR)

AF:

0.662

AC:

10116

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

2216

AN:

3466

East Asian (EAS)

AF:

0.790

AC:

4063

AN:

5140

South Asian (SAS)

AF:

0.740

AC:

3558

AN:

4810

European-Finnish (FIN)

AF:

0.596

AC:

6306

AN:

10578

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.602

AC:

40921

AN:

67974

Other (OTH)

AF:

0.697

AC:

1466

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1489

2978

4466

5955

7444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.633

Hom.:

135401

Bravo

AF:

0.723

TwinsUK

AF:

0.590

AC:

2188

ALSPAC

AF:

0.612

AC:

2358

ESP6500AA

AF:

0.924

AC:

4070

ESP6500EA

AF:

0.610

AC:

5243

ExAC

AF:

0.663

AC:

80494

Asia WGS

AF:

0.790

AC:

2748

AN:

3478

EpiCase

AF:

0.605

EpiControl

AF:

0.598

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 18, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Benign based on population frequency. There are a few association studies that claim a role in diseases unrelated to germline pulmonary diseases -

May 08, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30013576, 16741161, 21790524) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Benign

0.19

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.23

T;T

MetaRNN

Benign

0.0000025

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.40

N;.

PhyloP100

-2.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.63

N;N

REVEL

Benign

0.28

Sift

Benign

1.0

T;T

Sift4G

Benign

0.86

T;.

Polyphen

0.0

B;.

Vest4

0.010

MPC

0.17

ClinPred

0.0079

GERP RS

-3.8

Varity_R

0.046

gMVP

0.098

Mutation Taster

=99/1

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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rs2243639

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