chr20-3687178-A-G

Position:

• chr20-3687178-A-G

Variant summary

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

The ENST00000344754.6(SIGLEC1):​c.*1382T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,182 control chromosomes in the GnomAD database, including 2,937 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 (2936 hom., cov: 33)
  • Exomes 𝑓: 0.20 (1 hom.)
• Consequence: SIGLEC1 ENST00000344754.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.*1382T>C		3_prime_UTR_variant	22/22	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.*1333T>C		3_prime_UTR_variant	20/20		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.*1382T>C		3_prime_UTR_variant	22/22	1	NM_023068.4	ENSP00000341141	P2
SIGLEC1	ENST00000419548.4	c.*2728T>C		3_prime_UTR_variant	5/5	2		ENSP00000395778

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29352 AN: 152034 Hom.: 2929 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.200 AC: 6 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.136 AC XY: 3 AN XY: 22

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.193 AC: 29387 AN: 152152 Hom.: 2936 Cov.: 33 AF XY: 0.192 AC XY: 14298 AN XY: 74388

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.187

Alfa AF: 0.186 Hom.: 1774

Bravo AF: 0.189

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.79

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: rs1046919; hg19: chr20-3667825;