rs4987351

Variant names:

• chr1-169698214-T-A
• rs4987351
• NM_000655.5:c.1082-1661A>T

Variant summary

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

The NM_000655.5(SELL):​c.1082-1661A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,968 control chromosomes in the GnomAD database, including 18,996 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 0.50 (18996 hom., cov: 31)
• Consequence: SELL NM_000655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 5 publications found

Genes affected

SELL (HGNC:10720): (selectin L) This gene encodes a cell surface adhesion molecule that belongs to a family of adhesion/homing receptors. The encoded protein contains a C-type lectin-like domain, a calcium-binding epidermal growth factor-like domain, and two short complement-like repeats. The gene product is required for binding and subsequent rolling of leucocytes on endothelial cells, facilitating their migration into secondary lymphoid organs and inflammation sites. Single-nucleotide polymorphisms in this gene have been associated with various diseases including immunoglobulin A nephropathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELL	NM_000655.5	c.1082-1661A>T		intron_variant	Intron 7 of 8	ENST00000236147.6	NP_000646.3
SELL	NR_029467.2	n.1051-1661A>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELL	ENST00000236147.6	c.1082-1661A>T		intron_variant	Intron 7 of 8	1	NM_000655.5	ENSP00000236147.5
SELL	ENST00000650983.1	c.1121-1661A>T		intron_variant	Intron 7 of 8			ENSP00000498227.1
SELL	ENST00000497295.1	c.74-1661A>T		intron_variant	Intron 1 of 2	5		ENSP00000498707.1
FIRRM	ENST00000498289.5	n.851+14282T>A		intron_variant	Intron 3 of 28	2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75290 AN: 151850 Hom.: 18990 Cov.: 31

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.496 AC: 75319 AN: 151968 Hom.: 18996 Cov.: 31 AF XY: 0.495 AC XY: 36749 AN XY: 74294

African (AFR) AF: 0.546 AC: 22630 AN: 41422

American (AMR) AF: 0.452 AC: 6905 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1949 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2090 AN: 5170

South Asian (SAS) AF: 0.537 AC: 2591 AN: 4824

European-Finnish (FIN) AF: 0.428 AC: 4514 AN: 10552

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32984 AN: 67948

Other (OTH) AF: 0.503 AC: 1058 AN: 2102

Alfa AF: 0.495 Hom.: 2599

Bravo AF: 0.495

Asia WGS AF: 0.421 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.52
PhyloP100		0.39
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: rs4987351; hg19: chr1-169667355;