1-169600680-A-T

Variant names:

• chr1-169600680-A-T
• rs2420378
• NM_003005.4:c.1705+2346T>A

Variant summary

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

The NM_003005.4(SELP):​c.1705+2346T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,112 control chromosomes in the GnomAD database, including 11,659 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 0.34 (11659 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 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.1705+2346T>A		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.1705+2346T>A		intron	N/A	ENSP00000263686.5
	SELP	ENST00000426706.6	TSL:1	c.1702+2346T>A		intron	N/A	ENSP00000391694.2
	SELP	ENST00000367786.6	TSL:5	c.1519+2346T>A		intron	N/A	ENSP00000356760.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52436 AN: 151994 Hom.: 11654 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.345 AC: 52450 AN: 152112 Hom.: 11659 Cov.: 32 AF XY: 0.362 AC XY: 26886 AN XY: 74342

African (AFR) AF: 0.121 AC: 5039 AN: 41520

American (AMR) AF: 0.490 AC: 7481 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3468

East Asian (EAS) AF: 0.955 AC: 4947 AN: 5180

South Asian (SAS) AF: 0.528 AC: 2543 AN: 4814

European-Finnish (FIN) AF: 0.536 AC: 5667 AN: 10576

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24453 AN: 67980

Other (OTH) AF: 0.369 AC: 777 AN: 2104

Alfa AF: 0.352 Hom.: 1471

Bravo AF: 0.333

Asia WGS AF: 0.697 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.80
PhyloP100		0.20
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: rs2420378; hg19: chr1-169569918;