1-169707345-A-G

Position:

• chr1-169707345-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.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 same amino acid change has been previously reported as Likely benignin UniProt.

• 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]

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=0.0014271736).
• 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/exons	MANE	Protein	UniProt
SELL	NM_000655.5	c.577T>C	p.Phe193Leu	missense_variant	4/9	ENST00000236147.6	NP_000646.3
SELL	NR_029467.2	n.546T>C		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELL	ENST00000236147.6	c.577T>C	p.Phe193Leu	missense_variant	4/9	1	NM_000655.5	ENSP00000236147	P1

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
MutationTaster	Benign	1.0	P
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;