chr20-3704082-T-C

Variant names:

• chr20-3704082-T-C
• rs625372
• NM_023068.4:c.716A>G

Variant summary

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

The NM_023068.4(SIGLEC1):​c.716A>G​(p.Lys239Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,611,512 control chromosomes in the GnomAD database, including 332,206 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.63 (30205 hom., cov: 31)
  • Exomes 𝑓: 0.64 (302001 hom.)
• Consequence: SIGLEC1 NM_023068.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 28 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3265331E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 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.716A>G	p.Lys239Arg	missense	Exon 5 of 22	NP_075556.1	Q9BZZ2-1
	SIGLEC1	NM_001367089.1		c.716A>G	p.Lys239Arg	missense	Exon 4 of 20	NP_001354018.1	Q9BZZ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC1	ENST00000344754.6	TSL:1 MANE Select	c.716A>G	p.Lys239Arg	missense	Exon 5 of 22	ENSP00000341141.4	Q9BZZ2-1
	SIGLEC1	ENST00000869141.1		c.716A>G	p.Lys239Arg	missense	Exon 5 of 22	ENSP00000539200.1
	SIGLEC1	ENST00000869142.1		c.716A>G	p.Lys239Arg	missense	Exon 5 of 22	ENSP00000539201.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95440 AN: 151654 Hom.: 30169 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.623

GnomAD2 exomes AF: 0.644 AC: 160335 AN: 248878 AF XY: 0.647

Gnomad AFR exome AF: 0.567

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.669

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.656

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.642 AC: 936935 AN: 1459740 Hom.: 302001 Cov.: 50 AF XY: 0.642 AC XY: 466219 AN XY: 725982

African (AFR) AF: 0.570 AC: 19065 AN: 33450

American (AMR) AF: 0.598 AC: 26665 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 16641 AN: 26072

East Asian (EAS) AF: 0.683 AC: 27084 AN: 39664

South Asian (SAS) AF: 0.611 AC: 52631 AN: 86124

European-Finnish (FIN) AF: 0.741 AC: 39088 AN: 52746

Middle Eastern (MID) AF: 0.608 AC: 3500 AN: 5760

European-Non Finnish (NFE) AF: 0.642 AC: 713413 AN: 1111006

Other (OTH) AF: 0.644 AC: 38848 AN: 60310

GnomAD4 genome AF: 0.629 AC: 95517 AN: 151772 Hom.: 30205 Cov.: 31 AF XY: 0.637 AC XY: 47234 AN XY: 74198

African (AFR) AF: 0.571 AC: 23589 AN: 41346

American (AMR) AF: 0.627 AC: 9562 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2175 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3444 AN: 5130

South Asian (SAS) AF: 0.618 AC: 2966 AN: 4802

European-Finnish (FIN) AF: 0.749 AC: 7918 AN: 10578

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.649 AC: 44054 AN: 67878

Other (OTH) AF: 0.618 AC: 1304 AN: 2110

Alfa AF: 0.641 Hom.: 86285

Bravo AF: 0.613

Asia WGS AF: 0.629 AC: 2190 AN: 3478

EpiCase AF: 0.643

EpiControl AF: 0.645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
PhyloP100		-0.013
Varity_R		0.080
gMVP		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs625372; hg19: chr20-3684729; COSMIC: COSV52466532;