chr20-3699612-A-G

Variant names:

• chr20-3699612-A-G
• rs12624921
• NM_023068.4:c.1529-153T>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.1529-153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 152,274 control chromosomes in the GnomAD database, including 315 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 0.054 (315 hom., cov: 32)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.1529-153T>C		intron_variant	Intron 7 of 21	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.1529-153T>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.1529-153T>C		intron_variant	Intron 7 of 21	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1	c.1529-153T>C		intron_variant	Intron 6 of 19			ENSP00000516734.1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8191 AN: 152156 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0410

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0478

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

GnomAD4 genome AF: 0.0538 AC: 8192 AN: 152274 Hom.: 315 Cov.: 32 AF XY: 0.0544 AC XY: 4054 AN XY: 74466

African (AFR) AF: 0.0117 AC: 487 AN: 41570

American (AMR) AF: 0.0420 AC: 643 AN: 15294

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

East Asian (EAS) AF: 0.112 AC: 579 AN: 5168

South Asian (SAS) AF: 0.0177 AC: 85 AN: 4814

European-Finnish (FIN) AF: 0.0998 AC: 1060 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0741 AC: 5042 AN: 68026

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.0673 Hom.: 66

Bravo AF: 0.0476

Asia WGS AF: 0.0660 AC: 229 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	0.28
DANN	Benign	0.60
PhyloP100		-0.44
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: rs12624921; hg19: chr20-3680259;