rs4813636

Variant names:

• chr20-3701061-G-A
• rs4813636
• NM_023068.4:c.1528+281C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3701061-G-A
• chr20-3701061-G-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.1528+281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,072 control chromosomes in the GnomAD database, including 34,012 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 0.66 (34012 hom., cov: 32)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.1528+281C>T		intron_variant	Intron 7 of 21	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.1528+281C>T		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.1528+281C>T		intron_variant	Intron 7 of 21	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1	c.1528+281C>T		intron_variant	Intron 6 of 19			ENSP00000516734.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100776 AN: 151952 Hom.: 33995 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.663 AC: 100837 AN: 152072 Hom.: 34012 Cov.: 32 AF XY: 0.669 AC XY: 49739 AN XY: 74342

African (AFR) AF: 0.757 AC: 31415 AN: 41484

American (AMR) AF: 0.684 AC: 10443 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3472

East Asian (EAS) AF: 0.750 AC: 3871 AN: 5164

South Asian (SAS) AF: 0.747 AC: 3601 AN: 4822

European-Finnish (FIN) AF: 0.672 AC: 7101 AN: 10574

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40514 AN: 67974

Other (OTH) AF: 0.641 AC: 1352 AN: 2108

Alfa AF: 0.634 Hom.: 3815

Bravo AF: 0.666

Asia WGS AF: 0.704 AC: 2451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.31
PhyloP100		0.25
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: rs4813636; hg19: chr20-3681708;