20-3696367-C-T

Variant names:

• chr20-3696367-C-T
• rs525339
• NM_023068.4:c.2683+219G>A

Variant summary

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

The NM_023068.4(SIGLEC1):​c.2683+219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,034 control chromosomes in the GnomAD database, including 36,151 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 0.68 (36151 hom., cov: 32)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 3 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.2683+219G>A		intron_variant	Intron 11 of 21	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.2683+219G>A		intron_variant	Intron 10 of 19		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.2683+219G>A		intron_variant	Intron 11 of 21	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1	c.2683+219G>A		intron_variant	Intron 10 of 19			ENSP00000516734.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103978 AN: 151916 Hom.: 36102 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.685 AC: 104078 AN: 152034 Hom.: 36151 Cov.: 32 AF XY: 0.693 AC XY: 51465 AN XY: 74310

African (AFR) AF: 0.775 AC: 32146 AN: 41452

American (AMR) AF: 0.685 AC: 10464 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3468

East Asian (EAS) AF: 0.862 AC: 4464 AN: 5178

South Asian (SAS) AF: 0.706 AC: 3403 AN: 4820

European-Finnish (FIN) AF: 0.749 AC: 7896 AN: 10544

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41786 AN: 67972

Other (OTH) AF: 0.658 AC: 1392 AN: 2116

Alfa AF: 0.663 Hom.: 4210

Bravo AF: 0.682

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.68
PhyloP100		-0.020
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: rs525339; hg19: chr20-3677014; COSMIC: COSV52473413; COSMIC: COSV52473413;