Variant rs1051246 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003019.5(SFTPD):c.918T>C(p.Ala306Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,872 control chromosomes in the GnomAD database, including 17,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2553 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14844 hom. )

Consequence

SFTPD
NM_003019.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.53

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 10-79938062-A-G is Benign according to our data. Variant chr10-79938062-A-G is described in ClinVar as [Benign]. Clinvar id is 178808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5 link	c.918T>C	p.Ala306Ala	synonymous_variant	Exon 8 of 8	ENST00000372292.8	NP_003010.4	P35247
SFTPD	XM_011540087.2 link	c.918T>C	p.Ala306Ala	synonymous_variant	Exon 8 of 8		XP_011538389.1	P35247
SFTPD	XM_011540088.3 link	c.801T>C	p.Ala267Ala	synonymous_variant	Exon 7 of 7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8 link	c.918T>C	p.Ala306Ala	synonymous_variant	Exon 8 of 8	1	NM_003019.5	ENSP00000361366.3		P35247

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25295

AN:

151994

Hom.:

2540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0172

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.0606

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.157

AC:

39476

AN:

251466

Hom.:

4021

AF XY:

0.154

AC XY:

20874

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.0146

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.0703

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.134

AC:

195492

AN:

1461760

Hom.:

14844

Cov.:

AF XY:

0.135

AC XY:

98277

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.0709

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.167

AC:

25360

AN:

152112

Hom.:

2553

Cov.:

AF XY:

0.167

AC XY:

12395

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.272

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.0172

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.0606

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.145

Hom.:

2549

Bravo

AF:

0.184

Asia WGS

AF:

0.172

AC:

597

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Ala306Ala in exon 8 of SFTPD: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 22.9% (1010/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1051246). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.27

DANN

Benign

0.48

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

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