chr20-3699633-A-G

Variant names:

• chr20-3699633-A-G
• rs12624922
• NM_023068.4:c.1529-174T>C

Variant summary

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

The NM_023068.4(SIGLEC1):​c.1529-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 152,208 control chromosomes in the GnomAD database, including 365 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 0.065 (365 hom., cov: 32)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.1529-174T>C		intron_variant	Intron 7 of 21	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.1529-174T>C		intron_variant	Intron 6 of 19		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.1529-174T>C		intron_variant	Intron 7 of 21	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1	c.1529-174T>C		intron_variant	Intron 6 of 19			ENSP00000516734.1

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9845 AN: 152090 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0410

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0647 AC: 9850 AN: 152208 Hom.: 365 Cov.: 32 AF XY: 0.0649 AC XY: 4827 AN XY: 74420

African (AFR) AF: 0.0498 AC: 2070 AN: 41538

American (AMR) AF: 0.0460 AC: 703 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 142 AN: 3466

East Asian (EAS) AF: 0.112 AC: 582 AN: 5174

South Asian (SAS) AF: 0.0175 AC: 84 AN: 4812

European-Finnish (FIN) AF: 0.0997 AC: 1058 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0742 AC: 5045 AN: 68002

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0669 Hom.: 203

Bravo AF: 0.0598

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.48
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

Publications

LitVar

Other links and lift over

dbSNP: rs12624922; hg19: chr20-3680280;