rs6139180

Positions:

• chr20-3700636-A-G

Variant summary

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

The NM_023068.4(SIGLEC1):​c.1528+706T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 151,606 control chromosomes in the GnomAD database, including 919 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 0.094 (919 hom., cov: 29)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4	c.1528+706T>C		intron_variant		ENST00000344754.6
SIGLEC1	NM_001367089.1	c.1528+706T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.1528+706T>C		intron_variant		1	NM_023068.4	P2
SIGLEC1	ENST00000707083.1	c.1528+706T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14318 AN: 151490 Hom.: 920 Cov.: 29

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.0837

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.0924

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0945 AC: 14324 AN: 151606 Hom.: 919 Cov.: 29 AF XY: 0.0975 AC XY: 7213 AN XY: 73976

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.0931

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.104

Alfa AF: 0.102 Hom.: 1792

Bravo AF: 0.0895

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.6
DANN	Benign	0.87

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: rs6139180; hg19: chr20-3681283;