20-3687435-G-T

Variant summary

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

The NM_023068.4(SIGLEC1):c.*1125C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,084 control chromosomes in the GnomAD database, including 17,289 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 0.48 (17282 hom., cov: 32)
  • Exomes 𝑓: 0.48 (7 hom.)
• Consequence: SIGLEC1 NM_023068.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.*1125C>A		3_prime_UTR_variant	22/22	ENST00000344754.6
SIGLEC1	NM_001367089.1	c.*1076C>A		3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.*1125C>A		3_prime_UTR_variant	22/22	1	NM_023068.4	P2
SIGLEC1	ENST00000419548.4	c.*2471C>A		3_prime_UTR_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72291 AN: 151908 Hom.: 17276 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.483 AC: 29 AN: 60 Hom.: 7 Cov.: 0 AF XY: 0.531 AC XY: 17 AN XY: 32

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.476 AC: 72334 AN: 152024 Hom.: 17282 Cov.: 32 AF XY: 0.481 AC XY: 35765 AN XY: 74294

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.487

Alfa AF: 0.485 Hom.: 24838

Bravo AF: 0.475

Asia WGS AF: 0.413 AC: 1437 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	0.62
Dann	Benign	0.36

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: rs656635; hg19: chr20-3668082;