chr1-169621855-A-G

Variant names:

• chr1-169621855-A-G
• rs3917687
• NM_003005.4:c.4-2636T>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.4-2636T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,164 control chromosomes in the GnomAD database, including 3,515 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 0.19 (3515 hom., cov: 33)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 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.4-2636T>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.4-2636T>C		intron	N/A	ENSP00000263686.5
	SELP	ENST00000909597.1		c.4-2636T>C		intron	N/A	ENSP00000579656.1
	SELP	ENST00000909601.1		c.4-2636T>C		intron	N/A	ENSP00000579660.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29048 AN: 152046 Hom.: 3515 Cov.: 33

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.191 AC: 29047 AN: 152164 Hom.: 3515 Cov.: 33 AF XY: 0.185 AC XY: 13770 AN XY: 74406

African (AFR) AF: 0.0664 AC: 2755 AN: 41518

American (AMR) AF: 0.181 AC: 2771 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3470

East Asian (EAS) AF: 0.00617 AC: 32 AN: 5184

South Asian (SAS) AF: 0.135 AC: 649 AN: 4820

European-Finnish (FIN) AF: 0.202 AC: 2142 AN: 10592

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19023 AN: 67986

Other (OTH) AF: 0.213 AC: 450 AN: 2112

Alfa AF: 0.204 Hom.: 1256

Bravo AF: 0.183

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.32
PhyloP100		0.12
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: rs3917687; hg19: chr1-169591093;