rs3827110

Positions:

• chr20-3693417-G-C

Variant summary

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

The NM_023068.4(SIGLEC1):​c.3508+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,533,190 control chromosomes in the GnomAD database, including 9,191 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 0.14 (1725 hom., cov: 33)
  • Exomes 𝑓: 0.098 (7466 hom.)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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 (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.3508+30C>G		intron_variant		ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.3508+30C>G		intron_variant			NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.3508+30C>G		intron_variant		1	NM_023068.4	ENSP00000341141	P2
SIGLEC1	ENST00000707083.1	c.3508+30C>G		intron_variant				ENSP00000516734	A2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20527 AN: 152126 Hom.: 1712 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0726

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.0998 AC: 19197 AN: 192442 Hom.: 1200 AF XY: 0.0972 AC XY: 9996 AN XY: 102836

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.0536

Gnomad ASJ exome AF: 0.0463

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.0476

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.0979

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0983 AC: 135779 AN: 1380946 Hom.: 7466 Cov.: 32 AF XY: 0.0967 AC XY: 65497 AN XY: 677158

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.0559

Gnomad4 ASJ exome AF: 0.0499

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.0979

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.135 AC: 20585 AN: 152244 Hom.: 1725 Cov.: 33 AF XY: 0.133 AC XY: 9902 AN XY: 74446

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.106

Alfa AF: 0.110 Hom.: 244

Bravo AF: 0.136

Asia WGS AF: 0.0940 AC: 327 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	0.36
DANN	Benign	0.35

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: rs3827110; hg19: chr20-3674064; COSMIC: COSV52460701; COSMIC: COSV52460701;