rs2229569

Variant names:

• chr1-169704697-G-A
• rs2229569
• NM_000655.5:c.637C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169704697-G-A
• chr1-169704697-G-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.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.

• 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
• Publications: 37 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 (MetaRNN=0.0015850961).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000655.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELL	NM_000655.5	MANE Select	c.637C>T	p.Pro213Ser	missense	Exon 5 of 9	NP_000646.3	P14151-1
	SELL	NR_029467.2		n.606C>T		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELL	ENST00000236147.6	TSL:1 MANE Select	c.637C>T	p.Pro213Ser	missense	Exon 5 of 9	ENSP00000236147.5	P14151-1
	SELL	ENST00000463108.5	TSL:1	n.837C>T		non_coding_transcript_exon	Exon 5 of 7
	SELL	ENST00000650983.1		c.676C>T	p.Pro226Ser	missense	Exon 5 of 9	ENSP00000498227.1	P14151-2

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

GnomAD2 exomes AF: 0.206 AC: 32564 AN: 157854 AF XY: 0.202

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 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

African (AFR) AF: 0.249 AC: 7872 AN: 31604

American (AMR) AF: 0.323 AC: 11518 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4092 AN: 25184

East Asian (EAS) AF: 0.254 AC: 9097 AN: 35772

South Asian (SAS) AF: 0.238 AC: 18824 AN: 79246

European-Finnish (FIN) AF: 0.180 AC: 8877 AN: 49342

Middle Eastern (MID) AF: 0.239 AC: 1360 AN: 5690

European-Non Finnish (NFE) AF: 0.135 AC: 145574 AN: 1078754

Other (OTH) AF: 0.176 AC: 10222 AN: 58016

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

African (AFR) AF: 0.242 AC: 10042 AN: 41462

American (AMR) AF: 0.247 AC: 3772 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3466

East Asian (EAS) AF: 0.250 AC: 1291 AN: 5172

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1823 AN: 10582

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.137 AC: 9280 AN: 67982

Other (OTH) AF: 0.212 AC: 448 AN: 2110

Alfa AF: 0.159 Hom.: 7953

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 v4.9

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
PhyloP100		2.3
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
Mutation Taster		=84/16	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2229569; hg19: chr1-169673838; COSMIC: COSV52550378; COSMIC: COSV52550378;