rs2229569

chr1-169704697-G-Achr1-169704697-G-T

Variant summary

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

The NM_000655.5(SELL):c.637C>T(p.Pro213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,551,396 control chromosomes in the GnomAD database, including 21,682 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (2949 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18733 hom.)
• Consequence: SELL NM_000655.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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 (MetaRNN=0.0015850961).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELL	NM_000655.5	c.637C>T	p.Pro213Ser	missense_variant	5/9	ENST00000236147.6
SELL	NR_029467.2	n.606C>T		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELL	ENST00000236147.6	c.637C>T	p.Pro213Ser	missense_variant	5/9	1	NM_000655.5	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28514 AN: 151962 Hom.: 2937 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.206 AC: 32564 AN: 157854 Hom.: 3841 AF XY: 0.202 AC XY: 16773 AN XY: 83192

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.243

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.155 AC: 217436 AN: 1399316 Hom.: 18733 Cov.: 32 AF XY: 0.157 AC XY: 108635 AN XY: 690218

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.188 AC: 28571 AN: 152080 Hom.: 2949 Cov.: 32 AF XY: 0.190 AC XY: 14136 AN XY: 74342

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.212

Alfa AF: 0.152 Hom.: 3301

Bravo AF: 0.199

TwinsUK AF: 0.135 AC: 499

ALSPAC AF: 0.143 AC: 550

ESP6500AA AF: 0.218 AC: 809

ESP6500EA AF: 0.133 AC: 1076

ExAC AF: 0.125 AC: 10903

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.71	T
MutationTaster	Benign	0.0025	P
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.24
Sift	Benign	0.063	T
Sift4G	Benign	0.062	T
Vest4		0.040
MPC		0.079
ClinPred		0.029	T
GERP RS		5.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2229569; hg19: chr1-169673838; COSMIC: COSV52550378; COSMIC: COSV52550378;