rs4987382

Variant names:

• chr1-169691798-T-C
• rs4987382
• NM_000655.5:c.1105A>G

Variant summary

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

The NM_000655.5(SELL):​c.1105A>G​(p.Asn369Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00943 in 1,377,586 control chromosomes in the GnomAD database, including 856 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (535 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (321 hom.)
• Consequence: SELL NM_000655.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 10 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=0.0012456179).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 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.1105A>G	p.Asn369Asp	missense	Exon 9 of 9	NP_000646.3	P14151-1
	SELL	NR_029467.2		n.1074A>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELL	ENST00000236147.6	TSL:1 MANE Select	c.1105A>G	p.Asn369Asp	missense	Exon 9 of 9	ENSP00000236147.5	P14151-1
	SELL	ENST00000650983.1		c.1144A>G	p.Asn382Asp	missense	Exon 9 of 9	ENSP00000498227.1	P14151-2
	SELL	ENST00000878074.1		c.1105A>G	p.Asn369Asp	missense	Exon 10 of 10	ENSP00000548133.1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7168 AN: 152172 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0392

GnomAD2 exomes AF: 0.0126 AC: 1700 AN: 135144 AF XY: 0.00911

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.00731

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000926

Gnomad OTH exome AF: 0.00680

GnomAD4 exome AF: 0.00473 AC: 5800 AN: 1225296 Hom.: 321 Cov.: 24 AF XY: 0.00430 AC XY: 2584 AN XY: 601140

African (AFR) AF: 0.155 AC: 3853 AN: 24908

American (AMR) AF: 0.00849 AC: 163 AN: 19204

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 409 AN: 17744

East Asian (EAS) AF: 0.0000316 AC: 1 AN: 31686

South Asian (SAS) AF: 0.000232 AC: 11 AN: 47336

European-Finnish (FIN) AF: 0.0000225 AC: 1 AN: 44464

Middle Eastern (MID) AF: 0.00640 AC: 31 AN: 4846

European-Non Finnish (NFE) AF: 0.000727 AC: 717 AN: 985926

Other (OTH) AF: 0.0125 AC: 614 AN: 49182

GnomAD4 genome AF: 0.0472 AC: 7188 AN: 152290 Hom.: 535 Cov.: 32 AF XY: 0.0460 AC XY: 3422 AN XY: 74466

African (AFR) AF: 0.161 AC: 6667 AN: 41522

American (AMR) AF: 0.0185 AC: 283 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68038

Other (OTH) AF: 0.0388 AC: 82 AN: 2116

Alfa AF: 0.0207 Hom.: 493

Bravo AF: 0.0530

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.161 AC: 582

ESP6500EA AF: 0.00246 AC: 20

ExAC AF: 0.0148 AC: 1781

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.87
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.23
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.72	N
REVEL	Benign	0.078
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.013
MPC		0.019
ClinPred		0.0028	T
GERP RS		4.1
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: rs4987382; hg19: chr1-169660939;