Variant 20-3691476-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_023068.4(SIGLEC1):c.4455C>T(p.Asp1485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,613,472 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 21 hom. )

Consequence

SIGLEC1
NM_023068.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.831

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 20-3691476-G-A is Benign according to our data. Variant chr20-3691476-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652178.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.831 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC1	NM_023068.4 linkuse as main transcript	c.4455C>T	p.Asp1485=	synonymous_variant	18/22	ENST00000344754.6
SIGLEC1	NM_001367089.1 linkuse as main transcript	c.4455C>T	p.Asp1485=	synonymous_variant	17/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC1	ENST00000344754.6 linkuse as main transcript	c.4455C>T	p.Asp1485=	synonymous_variant	18/22	1	NM_023068.4	P2	Q9BZZ2-1
SIGLEC1	ENST00000707083.1 linkuse as main transcript	c.4455C>T	p.Asp1485=	synonymous_variant	17/20			A2
SIGLEC1	ENST00000419548.4 linkuse as main transcript	c.897C>T	p.Asp299=	synonymous_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

410

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00334

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00355

AC:

891

AN:

250664

Hom.:

AF XY:

0.00381

AC XY:

517

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.0345

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00297

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00343

AC:

5005

AN:

1461088

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2471

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.0320

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00263

Gnomad4 FIN exome

AF:

0.00121

Gnomad4 NFE exome

AF:

0.00315

Gnomad4 OTH exome

AF:

0.00459

GnomAD4 genome

AF:

0.00268

AC:

408

AN:

152384

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00104

Gnomad4 ASJ

AF:

0.0331

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00334

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00525

Hom.:

Bravo

AF:

0.00267

EpiCase

AF:

0.00267

EpiControl

AF:

0.00391

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SIGLEC1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.2

DANN

Benign

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over