rs1018493

Variant names:

• chr20-3701364-G-A
• rs1018493
• NM_023068.4:c.1506C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3701364-G-A
• chr20-3701364-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_023068.4(SIGLEC1):​c.1506C>T​(p.Ser502Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,611,836 control chromosomes in the GnomAD database, including 314,670 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 0.66 (34008 hom., cov: 33)
  • Exomes 𝑓: 0.62 (280662 hom.)
• Consequence: SIGLEC1 NM_023068.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 19 publications found

Genes affected

SIGLEC1 (HGNC:11127): (sialic acid binding Ig like lectin 1) This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in a sialic acid-dependent manner. It is a type I transmembrane protein expressed only by a subpopulation of macrophages and is involved in mediating cell-cell interactions. The protein plays an important role in multiple human diseases and bacterial and viral infections has been shown to enhance SARS-CoV-2 infection. [provided by RefSeq, Dec 2021]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.094 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.1506C>T	p.Ser502Ser	synonymous_variant	Exon 7 of 22	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.1506C>T	p.Ser502Ser	synonymous_variant	Exon 6 of 20		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.1506C>T	p.Ser502Ser	synonymous_variant	Exon 7 of 22	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1	c.1506C>T	p.Ser502Ser	synonymous_variant	Exon 6 of 20			ENSP00000516734.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100795 AN: 152022 Hom.: 33992 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.648

GnomAD2 exomes AF: 0.668 AC: 166058 AN: 248688 AF XY: 0.665

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.759

Gnomad FIN exome AF: 0.673

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.618 AC: 901401 AN: 1459696 Hom.: 280662 Cov.: 47 AF XY: 0.621 AC XY: 450796 AN XY: 725980

African (AFR) AF: 0.759 AC: 25403 AN: 33460

American (AMR) AF: 0.739 AC: 32985 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 15596 AN: 26020

East Asian (EAS) AF: 0.701 AC: 27804 AN: 39686

South Asian (SAS) AF: 0.739 AC: 63587 AN: 86080

European-Finnish (FIN) AF: 0.666 AC: 35528 AN: 53320

Middle Eastern (MID) AF: 0.621 AC: 3574 AN: 5758

European-Non Finnish (NFE) AF: 0.593 AC: 658820 AN: 1110450

Other (OTH) AF: 0.632 AC: 38104 AN: 60300

GnomAD4 genome AF: 0.663 AC: 100854 AN: 152140 Hom.: 34008 Cov.: 33 AF XY: 0.669 AC XY: 49749 AN XY: 74384

African (AFR) AF: 0.757 AC: 31419 AN: 41498

American (AMR) AF: 0.684 AC: 10455 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2042 AN: 3470

East Asian (EAS) AF: 0.749 AC: 3873 AN: 5170

South Asian (SAS) AF: 0.747 AC: 3605 AN: 4826

European-Finnish (FIN) AF: 0.670 AC: 7096 AN: 10588

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40515 AN: 67984

Other (OTH) AF: 0.641 AC: 1352 AN: 2108

Alfa AF: 0.625 Hom.: 80197

Bravo AF: 0.666

Asia WGS AF: 0.704 AC: 2450 AN: 3478

EpiCase AF: 0.596

EpiControl AF: 0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.0
DANN	Benign	0.65
PhyloP100		0.094
Mutation Taster		=45/55	disease causing

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: rs1018493; hg19: chr20-3682011; COSMIC: COSV52459251;