Genetic Variant SIGLEC1:c.2683+219G>A (chr20-3696367-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023068.4(SIGLEC1):c.2683+219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,034 control chromosomes in the GnomAD database, including 36,151 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 0.68 ( 36151 hom., cov: 32)

Consequence

SIGLEC1
NM_023068.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0200

Variant links:

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]

SIGLEC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 link	c.2683+219G>A		intron_variant	Intron 11 of 21	ENST00000344754.6	NP_075556.1	Q9BZZ2-1
SIGLEC1	NM_001367089.1 link	c.2683+219G>A		intron_variant	Intron 10 of 19		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6 link	c.2683+219G>A		intron_variant	Intron 11 of 21	1	NM_023068.4	ENSP00000341141.4		Q9BZZ2-1
SIGLEC1	ENST00000707083.1 link	c.2683+219G>A		intron_variant	Intron 10 of 19			ENSP00000516734.1		Q9BZZ2-3

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

103978

AN:

151916

Hom.:

36102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.862

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.749

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.615

Gnomad OTH

AF:

0.662

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

GnomAD4 genome

AF:

0.685

AC:

104078

AN:

152034

Hom.:

36151

Cov.:

AF XY:

0.693

AC XY:

51465

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.775

Gnomad4 AMR

AF:

0.685

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.862

Gnomad4 SAS

AF:

0.706

Gnomad4 FIN

AF:

0.749

Gnomad4 NFE

AF:

0.615

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.663

Hom.:

4210

Bravo

AF:

0.682

Asia WGS

AF:

0.755

AC:

2627

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.0

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over