rs4815596

Variant names:

• chr20-3691153-G-A
• rs4815596
• NM_023068.4:c.4591+187C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3691153-G-A
• chr20-3691153-G-T

Variant summary

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

The NM_023068.4(SIGLEC1):​c.4591+187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,084 control chromosomes in the GnomAD database, including 3,205 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 0.19 (3205 hom., cov: 31)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.4591+187C>T		intron_variant	Intron 18 of 21	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.4591+187C>T		intron_variant	Intron 17 of 19		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.4591+187C>T		intron_variant	Intron 18 of 21	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1	c.4591+187C>T		intron_variant	Intron 17 of 19			ENSP00000516734.1
SIGLEC1	ENST00000419548.4	c.1030+187C>T		intron_variant	Intron 4 of 4	2		ENSP00000395778.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29402 AN: 151966 Hom.: 3196 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.194 AC: 29433 AN: 152084 Hom.: 3205 Cov.: 31 AF XY: 0.194 AC XY: 14453 AN XY: 74350

African (AFR) AF: 0.287 AC: 11880 AN: 41448

American (AMR) AF: 0.128 AC: 1956 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1827 AN: 5164

South Asian (SAS) AF: 0.128 AC: 616 AN: 4818

European-Finnish (FIN) AF: 0.199 AC: 2102 AN: 10568

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10019 AN: 68010

Other (OTH) AF: 0.179 AC: 379 AN: 2112

Alfa AF: 0.161 Hom.: 1792

Bravo AF: 0.193

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.46
PhyloP100		0.019
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: rs4815596; hg19: chr20-3671800;