chr20-3712192-T-C

Variant names:

• chr20-3712192-T-C
• rs735710
• NM_023068.4:c.-110+278A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023068.4(SIGLEC1):​c.-110+278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 141,174 control chromosomes in the GnomAD database, including 558 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 0.086 (558 hom., cov: 29)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 3 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]

ENSG00000297858 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4	c.-110+278A>G		intron_variant	Intron 1 of 21	ENST00000344754.6	NP_075556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6	c.-110+278A>G		intron_variant	Intron 1 of 21	1	NM_023068.4	ENSP00000341141.4
ENSG00000297858	ENST00000751418.1	n.312-259T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 12098 AN: 141042 Hom.: 557 Cov.: 29

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0523

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0471

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.0238

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0858 AC: 12109 AN: 141174 Hom.: 558 Cov.: 29 AF XY: 0.0856 AC XY: 5883 AN XY: 68730

African (AFR) AF: 0.0890 AC: 3369 AN: 37838

American (AMR) AF: 0.121 AC: 1712 AN: 14204

Ashkenazi Jewish (ASJ) AF: 0.0471 AC: 157 AN: 3332

East Asian (EAS) AF: 0.136 AC: 604 AN: 4444

South Asian (SAS) AF: 0.0238 AC: 96 AN: 4040

European-Finnish (FIN) AF: 0.0795 AC: 732 AN: 9212

Middle Eastern (MID) AF: 0.0210 AC: 5 AN: 238

European-Non Finnish (NFE) AF: 0.0804 AC: 5230 AN: 65026

Other (OTH) AF: 0.0801 AC: 160 AN: 1998

Alfa AF: 0.0750 Hom.: 724

Bravo AF: 0.0849

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		-0.43
PromoterAI		0.0093	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs735710; hg19: chr20-3692839;