rs1051246

Variant names:

• chr10-79938062-A-G
• rs1051246
• NM_003019.5:c.918T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.53
• Publications: 25 publications found

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]

ENSG00000283913 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	c.918T>C	p.Ala306Ala	synonymous_variant	Exon 8 of 8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.918T>C	p.Ala306Ala	synonymous_variant	Exon 8 of 8		XP_011538389.1
SFTPD	XM_011540088.3	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	c.918T>C	p.Ala306Ala	synonymous_variant	Exon 8 of 8	1	NM_003019.5	ENSP00000361366.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25295 AN: 151994 Hom.: 2540 Cov.: 32

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

GnomAD2 exomes AF: 0.157 AC: 39476 AN: 251466 AF XY: 0.154

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 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.: 33 AF XY: 0.135 AC XY: 98277 AN XY: 727154

African (AFR) AF: 0.242 AC: 8110 AN: 33480

American (AMR) AF: 0.292 AC: 13060 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6541 AN: 26134

East Asian (EAS) AF: 0.0224 AC: 888 AN: 39700

South Asian (SAS) AF: 0.202 AC: 17391 AN: 86256

European-Finnish (FIN) AF: 0.0709 AC: 3786 AN: 53418

Middle Eastern (MID) AF: 0.228 AC: 1316 AN: 5768

European-Non Finnish (NFE) AF: 0.121 AC: 135027 AN: 1111892

Other (OTH) AF: 0.155 AC: 9373 AN: 60390

GnomAD4 genome AF: 0.167 AC: 25360 AN: 152112 Hom.: 2553 Cov.: 32 AF XY: 0.167 AC XY: 12395 AN XY: 74364

African (AFR) AF: 0.237 AC: 9844 AN: 41460

American (AMR) AF: 0.272 AC: 4160 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3472

East Asian (EAS) AF: 0.0172 AC: 89 AN: 5166

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4828

European-Finnish (FIN) AF: 0.0606 AC: 642 AN: 10598

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8158 AN: 67994

Other (OTH) AF: 0.194 AC: 409 AN: 2108

Alfa AF: 0.143 Hom.: 3244

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

Submissions by phenotype

not specified Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

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
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.48
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051246; hg19: chr10-81697818; COSMIC: COSV64852759; COSMIC: COSV64852759;