1-169623273-A-C

Variant names:

• chr1-169623273-A-C
• rs3917676
• NM_003005.4:c.4-4054T>G

Variant summary

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

The NM_003005.4(SELP):​c.4-4054T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 152,182 control chromosomes in the GnomAD database, including 205 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 0.044 (205 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.863
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.118 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.4-4054T>G		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.4-4054T>G		intron	N/A	ENSP00000263686.5
	SELP	ENST00000367786.6	TSL:5	c.4-4054T>G		intron	N/A	ENSP00000356760.1
	SELP	ENST00000367788.6	TSL:5	c.4-4054T>G		intron	N/A	ENSP00000356762.1

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6651 AN: 152064 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0440

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0438 AC: 6665 AN: 152182 Hom.: 205 Cov.: 32 AF XY: 0.0462 AC XY: 3436 AN XY: 74408

African (AFR) AF: 0.0321 AC: 1331 AN: 41522

American (AMR) AF: 0.0720 AC: 1102 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3472

East Asian (EAS) AF: 0.126 AC: 651 AN: 5184

South Asian (SAS) AF: 0.0440 AC: 212 AN: 4818

European-Finnish (FIN) AF: 0.0388 AC: 410 AN: 10570

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0391 AC: 2657 AN: 68000

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0424 Hom.: 50

Bravo AF: 0.0457

Asia WGS AF: 0.0620 AC: 218 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	4.4
DANN	Benign	0.77
PhyloP100		0.86
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: rs3917676; hg19: chr1-169592511;