rs6132

Variant names:

• chr1-169597070-G-A
• rs6132
• NM_003005.4:c.1812C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169597070-G-A
• chr1-169597070-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003005.4(SELP):​c.1812C>T​(p.Asn604Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,607,026 control chromosomes in the GnomAD database, including 22,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (7128 hom., cov: 33)
  • Exomes 𝑓: 0.12 (14923 hom.)
• Consequence: SELP NM_003005.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.429
• Publications: 10 publications found

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-169597070-G-A is Benign according to our data. Variant chr1-169597070-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055528.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.429 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003005.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	NM_003005.4	MANE Select	c.1812C>T	p.Asn604Asn	synonymous	Exon 11 of 17	NP_002996.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	ENST00000263686.11	TSL:1 MANE Select	c.1812C>T	p.Asn604Asn	synonymous	Exon 11 of 17	ENSP00000263686.5
	SELP	ENST00000426706.6	TSL:1	c.1809C>T	p.Asn603Asn	synonymous	Exon 10 of 15	ENSP00000391694.2
	SELP	ENST00000367786.6	TSL:5	c.1626C>T	p.Asn542Asn	synonymous	Exon 10 of 16	ENSP00000356760.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34692 AN: 151940 Hom.: 7114 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.199

GnomAD2 exomes AF: 0.113 AC: 27871 AN: 247458 AF XY: 0.102

Gnomad AFR exome AF: 0.567

Gnomad AMR exome AF: 0.0908

Gnomad ASJ exome AF: 0.0857

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0766

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.117 AC: 170837 AN: 1454968 Hom.: 14923 Cov.: 30 AF XY: 0.113 AC XY: 81767 AN XY: 723890

African (AFR) AF: 0.571 AC: 18652 AN: 32684

American (AMR) AF: 0.0983 AC: 4334 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 2328 AN: 25844

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39686

South Asian (SAS) AF: 0.0235 AC: 2020 AN: 85814

European-Finnish (FIN) AF: 0.0796 AC: 4232 AN: 53154

Middle Eastern (MID) AF: 0.127 AC: 727 AN: 5726

European-Non Finnish (NFE) AF: 0.118 AC: 130420 AN: 1107974

Other (OTH) AF: 0.135 AC: 8109 AN: 59988

GnomAD4 genome AF: 0.229 AC: 34752 AN: 152058 Hom.: 7128 Cov.: 33 AF XY: 0.220 AC XY: 16368 AN XY: 74348

African (AFR) AF: 0.555 AC: 22986 AN: 41398

American (AMR) AF: 0.143 AC: 2181 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4824

European-Finnish (FIN) AF: 0.0770 AC: 816 AN: 10604

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7875 AN: 67992

Other (OTH) AF: 0.200 AC: 422 AN: 2110

Alfa AF: 0.212 Hom.: 4791

Bravo AF: 0.252

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SELP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.52
PhyloP100		-0.43
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: rs6132; hg19: chr1-169566308; COSMIC: COSV55255401;