rs4813636

Positions:

• chr20-3701061-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.1528+281C>T		intron_variant		ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.1528+281C>T		intron_variant			NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.1528+281C>T		intron_variant		1	NM_023068.4	ENSP00000341141	P2
SIGLEC1	ENST00000707083.1	c.1528+281C>T		intron_variant				ENSP00000516734	A2

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

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.641

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

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: rs4813636; hg19: chr20-3681708;