rs754526

Positions:

• chr20-3695252-T-A
• chr20-3695252-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023068.4(SIGLEC1):​c.2684-329A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 152,246 control chromosomes in the GnomAD database, including 311 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 (311 hom., cov: 32)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-0.87).
• 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/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.2684-329A>T		intron_variant		ENST00000344754.6
SIGLEC1	NM_001367089.1	c.2684-329A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.2684-329A>T		intron_variant		1	NM_023068.4	P2
SIGLEC1	ENST00000707083.1	c.2684-329A>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8153 AN: 152128 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0536 AC: 8154 AN: 152246 Hom.: 311 Cov.: 32 AF XY: 0.0542 AC XY: 4036 AN XY: 74440

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0678 Hom.: 53

Bravo AF: 0.0474

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	-0.87
CADD	Benign	0.91
DANN	Benign	0.60

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: rs754526; hg19: chr20-3675899;