rs12938

chr1-169691640-A-G

Variant summary

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

The NM_000655.5(SELL):c.*144T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 413,822 control chromosomes in the GnomAD database, including 14,809 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 0.27 (5715 hom., cov: 31)
  • Exomes 𝑓: 0.25 (9094 hom.)
• Consequence: SELL NM_000655.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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 = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELL	NM_000655.5	c.*144T>C		3_prime_UTR_variant	9/9	ENST00000236147.6
SELL	NR_029467.2	n.1232T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELL	ENST00000236147.6	c.*144T>C		3_prime_UTR_variant	9/9	1	NM_000655.5	P1
SELL	ENST00000650983.1	c.*144T>C		3_prime_UTR_variant	9/9
FIRRM	ENST00000498289.5	n.851+7708A>G		intron_variant, non_coding_transcript_variant		2
SELL	ENST00000497295.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40454 AN: 151956 Hom.: 5715 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.252 AC: 65992 AN: 261750 Hom.: 9094 Cov.: 5 AF XY: 0.253 AC XY: 33258 AN XY: 131622

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.0410

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.266 AC: 40458 AN: 152072 Hom.: 5715 Cov.: 31 AF XY: 0.262 AC XY: 19479 AN XY: 74352

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0606

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.254

Alfa AF: 0.271 Hom.: 9532

Bravo AF: 0.265

Asia WGS AF: 0.124 AC: 432 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	0.14
Dann	Benign	0.43

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: rs12938; hg19: chr1-169660781; COSMIC: COSV52550651; COSMIC: COSV52550651;