20-3703375-A-G

Variant names:

• chr20-3703375-A-G
• rs611847
• NM_023068.4:c.1050T>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.1050T>C​(p.Asn350Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,612,216 control chromosomes in the GnomAD database, including 332,927 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 0.63 (30420 hom., cov: 32)
  • Exomes 𝑓: 0.64 (302507 hom.)
• Consequence: SIGLEC1 NM_023068.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• Publications: 22 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=-0.92).
• BP7: Synonymous conserved (PhyloP=-3.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023068.4. 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
	SIGLEC1	NM_023068.4	MANE Select	c.1050T>C	p.Asn350Asn	synonymous	Exon 6 of 22	NP_075556.1
	SIGLEC1	NM_001367089.1		c.1050T>C	p.Asn350Asn	synonymous	Exon 5 of 20	NP_001354018.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC1	ENST00000344754.6	TSL:1 MANE Select	c.1050T>C	p.Asn350Asn	synonymous	Exon 6 of 22	ENSP00000341141.4
	SIGLEC1	ENST00000869141.1		c.1050T>C	p.Asn350Asn	synonymous	Exon 6 of 22	ENSP00000539200.1
	SIGLEC1	ENST00000869142.1		c.1050T>C	p.Asn350Asn	synonymous	Exon 6 of 22	ENSP00000539201.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95861 AN: 151962 Hom.: 30383 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.622

GnomAD2 exomes AF: 0.645 AC: 161277 AN: 249904 AF XY: 0.647

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.596

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.670

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.655

Gnomad OTH exome AF: 0.650

GnomAD4 exome AF: 0.642 AC: 937973 AN: 1460136 Hom.: 302507 Cov.: 50 AF XY: 0.643 AC XY: 466721 AN XY: 726224

African (AFR) AF: 0.578 AC: 19343 AN: 33474

American (AMR) AF: 0.600 AC: 26749 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 16586 AN: 26006

East Asian (EAS) AF: 0.683 AC: 27114 AN: 39682

South Asian (SAS) AF: 0.612 AC: 52610 AN: 85974

European-Finnish (FIN) AF: 0.741 AC: 39554 AN: 53368

Middle Eastern (MID) AF: 0.609 AC: 3506 AN: 5758

European-Non Finnish (NFE) AF: 0.642 AC: 713611 AN: 1110960

Other (OTH) AF: 0.645 AC: 38900 AN: 60316

GnomAD4 genome AF: 0.631 AC: 95940 AN: 152080 Hom.: 30420 Cov.: 32 AF XY: 0.638 AC XY: 47462 AN XY: 74368

African (AFR) AF: 0.576 AC: 23886 AN: 41448

American (AMR) AF: 0.627 AC: 9584 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2172 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3477 AN: 5170

South Asian (SAS) AF: 0.618 AC: 2979 AN: 4818

European-Finnish (FIN) AF: 0.748 AC: 7938 AN: 10606

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

European-Non Finnish (NFE) AF: 0.649 AC: 44093 AN: 67958

Other (OTH) AF: 0.618 AC: 1307 AN: 2116

Alfa AF: 0.639 Hom.: 138156

Bravo AF: 0.615

Asia WGS AF: 0.631 AC: 2196 AN: 3478

EpiCase AF: 0.643

EpiControl AF: 0.646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.26
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs611847; hg19: chr20-3684022; COSMIC: COSV52466517;