1-169594892-T-G

Variant names:

• chr1-169594892-T-G
• rs1569471
• NM_003005.4:c.2102-15A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003005.4(SELP):​c.2102-15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,602,256 control chromosomes in the GnomAD database, including 45,010 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (9168 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35842 hom.)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 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.2102-15A>C		intron	N/A	NP_002996.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	ENST00000263686.11	TSL:1 MANE Select	c.2102-15A>C		intron	N/A	ENSP00000263686.5
	SELP	ENST00000426706.6	TSL:1	c.2099-15A>C		intron	N/A	ENSP00000391694.2
	SELP	ENST00000367786.6	TSL:5	c.1916-15A>C		intron	N/A	ENSP00000356760.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45133 AN: 152012 Hom.: 9153 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.280

GnomAD2 exomes AF: 0.190 AC: 47024 AN: 247080 AF XY: 0.182

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.00855

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.207 AC: 300204 AN: 1450124 Hom.: 35842 Cov.: 30 AF XY: 0.202 AC XY: 145672 AN XY: 720114

African (AFR) AF: 0.591 AC: 19579 AN: 33150

American (AMR) AF: 0.154 AC: 6768 AN: 44024

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5273 AN: 25852

East Asian (EAS) AF: 0.0118 AC: 468 AN: 39516

South Asian (SAS) AF: 0.0781 AC: 6665 AN: 85386

European-Finnish (FIN) AF: 0.150 AC: 7978 AN: 53184

Middle Eastern (MID) AF: 0.219 AC: 1247 AN: 5700

European-Non Finnish (NFE) AF: 0.217 AC: 239175 AN: 1103508

Other (OTH) AF: 0.218 AC: 13051 AN: 59804

GnomAD4 genome AF: 0.297 AC: 45189 AN: 152132 Hom.: 9168 Cov.: 33 AF XY: 0.286 AC XY: 21271 AN XY: 74376

African (AFR) AF: 0.576 AC: 23903 AN: 41480

American (AMR) AF: 0.207 AC: 3167 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3468

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5178

South Asian (SAS) AF: 0.0746 AC: 360 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10606

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14779 AN: 67986

Other (OTH) AF: 0.279 AC: 588 AN: 2108

Alfa AF: 0.250 Hom.: 2826

Bravo AF: 0.317

Asia WGS AF: 0.0930 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		-0.32
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: rs1569471; hg19: chr1-169564130; COSMIC: COSV55248035; COSMIC: COSV55248035;