1-169593711-A-G

Variant names:

• chr1-169593711-A-G
• rs3917831
• NM_003005.4:c.2301T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003005.4(SELP):​c.2301T>C​(p.Thr767Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,510 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (31 hom.)
• Consequence: SELP NM_003005.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.663

Genes affected

SELP (HGNC:10721): (selectin P) This gene encodes a 140 kDa protein that is stored in the alpha-granules of platelets and Weibel-Palade bodies of endothelial cells. This protein redistributes to the plasma membrane during platelet activation and degranulation and mediates the interaction of activated endothelial cells or platelets with leukocytes. The membrane protein is a calcium-dependent receptor that binds to sialylated forms of Lewis blood group carbohydrate antigens on neutrophils and monocytes. Alternative splice variants may occur but are not well documented. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.014).
• BP6: Variant 1-169593711-A-G is Benign according to our data. Variant chr1-169593711-A-G is described in ClinVar as [Benign]. Clinvar id is 775623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.663 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1596/152332) while in subpopulation AFR AF = 0.035 (1456/41566). AF 95% confidence interval is 0.0335. There are 26 homozygotes in GnomAd4. There are 756 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.2301T>C	p.Thr767Thr	synonymous_variant	Exon 14 of 17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.2301T>C	p.Thr767Thr	synonymous_variant	Exon 14 of 17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1597 AN: 152214 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00297 AC: 746 AN: 250996 AF XY: 0.00220

Gnomad AFR exome AF: 0.0375

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00129 AC: 1887 AN: 1461178 Hom.: 31 Cov.: 31 AF XY: 0.00110 AC XY: 799 AN XY: 726912

Gnomad4 AFR exome AF: 0.0380 AC: 1270 AN: 33448

Gnomad4 AMR exome AF: 0.00289 AC: 129 AN: 44674

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26096

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39676

Gnomad4 SAS exome AF: 0.0000696 AC: 6 AN: 86228

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53396

Gnomad4 NFE exome AF: 0.000291 AC: 324 AN: 1111524

Gnomad4 Remaining exome AF: 0.00247 AC: 149 AN: 60372

GnomAD4 genome AF: 0.0105 AC: 1596 AN: 152332 Hom.: 26 Cov.: 32 AF XY: 0.0101 AC XY: 756 AN XY: 74500

Gnomad4 AFR AF: 0.0350 AC: 0.0350286 AN: 0.0350286

Gnomad4 AMR AF: 0.00739 AC: 0.00738562 AN: 0.00738562

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000162 AC: 0.000161698 AN: 0.000161698

Gnomad4 OTH AF: 0.00758 AC: 0.00757576 AN: 0.00757576

Alfa AF: 0.00418 Hom.: 16

Bravo AF: 0.0118

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.38
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs3917831; hg19: chr1-169562949;