chr1-169707345-A-G

Variant names:

• chr1-169707345-A-G
• rs1131498
• NM_000655.5:c.577T>C

Variant summary

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

The NM_000655.5(SELL):​c.577T>C​(p.Phe193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,607,898 control chromosomes in the GnomAD database, including 51,524 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F193Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3854 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47670 hom.)
• Consequence: SELL NM_000655.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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]

C1orf112 (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=0.0014271736).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELL	NM_000655.5	c.577T>C	p.Phe193Leu	missense_variant	Exon 4 of 9	ENST00000236147.6	NP_000646.3
SELL	NR_029467.2	n.546T>C		non_coding_transcript_exon_variant	Exon 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELL	ENST00000236147.6	c.577T>C	p.Phe193Leu	missense_variant	Exon 4 of 9	1	NM_000655.5	ENSP00000236147.5

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32356 AN: 151898 Hom.: 3855 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.206 AC: 50921 AN: 247268 Hom.: 6079 AF XY: 0.211 AC XY: 28323 AN XY: 134154

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.00549

Gnomad SAS exome AF: 0.163

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.249 AC: 361860 AN: 1455882 Hom.: 47670 Cov.: 29 AF XY: 0.247 AC XY: 179173 AN XY: 724332

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.00404

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.213 AC: 32343 AN: 152016 Hom.: 3854 Cov.: 32 AF XY: 0.207 AC XY: 15406 AN XY: 74296

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.00522

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.225

Alfa AF: 0.254 Hom.: 8877

Bravo AF: 0.210

TwinsUK AF: 0.275 AC: 1021

ALSPAC AF: 0.265 AC: 1021

ESP6500AA AF: 0.143 AC: 541

ESP6500EA AF: 0.267 AC: 2204

ExAC AF: 0.207 AC: 25050

Asia WGS AF: 0.0600 AC: 207 AN: 3478

EpiCase AF: 0.280

EpiControl AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.64	T
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.29
Sift	Benign	0.38	T
Sift4G	Benign	0.37	T
Vest4		0.13
MPC		0.021
ClinPred		0.014	T
GERP RS		3.2

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: rs1131498; hg19: chr1-169676486;