rs4987361

Positions:

• chr1-169695241-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000655.5(SELL):​c.1100+1294C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,188 control chromosomes in the GnomAD database, including 1,624 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 0.11 (1624 hom., cov: 32)
• Consequence: SELL NM_000655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELL	NM_000655.5	c.1100+1294C>G		intron_variant		ENST00000236147.6
SELL	NR_029467.2	n.1069+1294C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELL	ENST00000236147.6	c.1100+1294C>G		intron_variant		1	NM_000655.5	P1
SELL	ENST00000497295.1	c.94+1294C>G		intron_variant		5
SELL	ENST00000650983.1	c.1139+1294C>G		intron_variant
FIRRM	ENST00000498289.5	n.851+11309G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16056 AN: 152070 Hom.: 1615 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0414

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0405

Gnomad OTH AF: 0.0998

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

GnomAD4 genome AF: 0.106 AC: 16097 AN: 152188 Hom.: 1624 Cov.: 32 AF XY: 0.104 AC XY: 7776 AN XY: 74418

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0594

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.0415

Gnomad4 SAS AF: 0.0953

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.0405

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0740 Hom.: 120

Bravo AF: 0.115

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs4987361; hg19: chr1-169664382;