chr1-169696491-T-C

Variant names:

• chr1-169696491-T-C
• rs2223286
• NM_000655.5:c.1100+44A>G

Variant summary

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

The NM_000655.5(SELL):​c.1100+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,547,900 control chromosomes in the GnomAD database, including 81,722 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 0.37 (12204 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69518 hom.)
• Consequence: SELL NM_000655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938
• Publications: 42 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELL	NM_000655.5	c.1100+44A>G		intron_variant	Intron 8 of 8	ENST00000236147.6	NP_000646.3
SELL	NR_029467.2	n.1069+44A>G		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELL	ENST00000236147.6	c.1100+44A>G		intron_variant	Intron 8 of 8	1	NM_000655.5	ENSP00000236147.5
SELL	ENST00000650983.1	c.1139+44A>G		intron_variant	Intron 8 of 8			ENSP00000498227.1
SELL	ENST00000497295.1	c.92+44A>G		intron_variant	Intron 2 of 2	5		ENSP00000498707.1
FIRRM	ENST00000498289.5	n.851+12559T>C		intron_variant	Intron 3 of 28	2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56428 AN: 151954 Hom.: 12194 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.293 AC: 47820 AN: 163314 AF XY: 0.295

Gnomad AFR exome AF: 0.604

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.108

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.310

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.308 AC: 429749 AN: 1395828 Hom.: 69518 Cov.: 29 AF XY: 0.309 AC XY: 212617 AN XY: 689110

African (AFR) AF: 0.605 AC: 19123 AN: 31632

American (AMR) AF: 0.201 AC: 7242 AN: 36070

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8152 AN: 25178

East Asian (EAS) AF: 0.0863 AC: 3128 AN: 36244

South Asian (SAS) AF: 0.341 AC: 27053 AN: 79282

European-Finnish (FIN) AF: 0.257 AC: 12684 AN: 49330

Middle Eastern (MID) AF: 0.388 AC: 2207 AN: 5686

European-Non Finnish (NFE) AF: 0.309 AC: 332112 AN: 1074452

Other (OTH) AF: 0.311 AC: 18048 AN: 57954

GnomAD4 genome AF: 0.371 AC: 56476 AN: 152072 Hom.: 12204 Cov.: 32 AF XY: 0.366 AC XY: 27231 AN XY: 74316

African (AFR) AF: 0.593 AC: 24587 AN: 41476

American (AMR) AF: 0.265 AC: 4056 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1101 AN: 3466

East Asian (EAS) AF: 0.102 AC: 527 AN: 5182

South Asian (SAS) AF: 0.330 AC: 1589 AN: 4818

European-Finnish (FIN) AF: 0.258 AC: 2720 AN: 10560

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20843 AN: 67964

Other (OTH) AF: 0.360 AC: 759 AN: 2110

Alfa AF: 0.326 Hom.: 34509

Bravo AF: 0.380

Asia WGS AF: 0.232 AC: 807 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.50
PhyloP100		-0.94
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: rs2223286; hg19: chr1-169665632; COSMIC: COSV52550669;