NM_000655.5:c.953-649A>C

Variant names:

• chr1-169702337-T-G
• rs4987318
• NM_000655.5:c.953-649A>C

Variant summary

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

The NM_000655.5(SELL):​c.953-649A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,072 control chromosomes in the GnomAD database, including 7,490 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 0.31 (7490 hom., cov: 32)
• Consequence: SELL NM_000655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 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.953-649A>C		intron	N/A	NP_000646.3	P14151-1
	SELL	NR_029467.2		n.922-649A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELL	ENST00000236147.6	TSL:1 MANE Select	c.953-649A>C		intron	N/A	ENSP00000236147.5	P14151-1
	SELL	ENST00000463108.5	TSL:1	n.1153-649A>C		intron	N/A
	SELL	ENST00000650983.1		c.992-649A>C		intron	N/A	ENSP00000498227.1	P14151-2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46761 AN: 151954 Hom.: 7458 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.308 AC: 46852 AN: 152072 Hom.: 7490 Cov.: 32 AF XY: 0.310 AC XY: 23054 AN XY: 74324

African (AFR) AF: 0.377 AC: 15632 AN: 41456

American (AMR) AF: 0.332 AC: 5066 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1728 AN: 5176

South Asian (SAS) AF: 0.415 AC: 1999 AN: 4820

European-Finnish (FIN) AF: 0.268 AC: 2831 AN: 10568

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17328 AN: 67990

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.263 Hom.: 1843

Bravo AF: 0.316

Asia WGS AF: 0.382 AC: 1329 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-0.35
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: rs4987318; hg19: chr1-169671478;