rs6139180

Variant names:

• chr20-3700636-A-G
• rs6139180
• NM_023068.4:c.1528+706T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.1528+706T>C		intron_variant	Intron 7 of 21	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1	c.1528+706T>C		intron_variant	Intron 6 of 19		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.1528+706T>C		intron_variant	Intron 7 of 21	1	NM_023068.4	ENSP00000341141.4
SIGLEC1	ENST00000707083.1	c.1528+706T>C		intron_variant	Intron 6 of 19			ENSP00000516734.1

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

African (AFR) AF: 0.0406 AC: 1681 AN: 41420

American (AMR) AF: 0.0864 AC: 1314 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1708 AN: 5116

South Asian (SAS) AF: 0.0931 AC: 447 AN: 4800

European-Finnish (FIN) AF: 0.145 AC: 1502 AN: 10376

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7206 AN: 67912

Other (OTH) AF: 0.104 AC: 219 AN: 2106

Alfa AF: 0.0992 Hom.: 2942

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
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6139180; hg19: chr20-3681283;