rs17701662

Positions:

• chr20-3689865-A-T

Variant summary

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

The NM_023068.4(SIGLEC1):​c.4894+97T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,215,546 control chromosomes in the GnomAD database, including 2,163 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 0.043 (208 hom., cov: 33)
  • Exomes 𝑓: 0.056 (1955 hom.)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.4894+97T>A		intron_variant		ENST00000344754.6
SIGLEC1	NM_001367089.1	c.4894+97T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.4894+97T>A		intron_variant		1	NM_023068.4	P2
SIGLEC1	ENST00000419548.4	c.*41T>A		3_prime_UTR_variant	5/5	2
SIGLEC1	ENST00000707083.1	c.4894+97T>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6592 AN: 152208 Hom.: 208 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00889

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0421

GnomAD3 exomes AF: 0.0422 AC: 5909 AN: 140104 Hom.: 173 AF XY: 0.0414 AC XY: 3062 AN XY: 73894

Gnomad AFR exome AF: 0.00764

Gnomad AMR exome AF: 0.0327

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00664

Gnomad FIN exome AF: 0.0766

Gnomad NFE exome AF: 0.0641

Gnomad OTH exome AF: 0.0483

GnomAD4 exome AF: 0.0562 AC: 59788 AN: 1063220 Hom.: 1955 Cov.: 14 AF XY: 0.0549 AC XY: 29332 AN XY: 534228

Gnomad4 AFR exome AF: 0.00882

Gnomad4 AMR exome AF: 0.0332

Gnomad4 ASJ exome AF: 0.0373

Gnomad4 EAS exome AF: 0.000147

Gnomad4 SAS exome AF: 0.00771

Gnomad4 FIN exome AF: 0.0771

Gnomad4 NFE exome AF: 0.0654

Gnomad4 OTH exome AF: 0.0491

GnomAD4 genome AF: 0.0433 AC: 6592 AN: 152326 Hom.: 208 Cov.: 33 AF XY: 0.0423 AC XY: 3152 AN XY: 74484

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0417

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0487 Hom.: 46

Bravo AF: 0.0396

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.40

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: rs17701662; hg19: chr20-3670512;