Variant rs3746638 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000344754.6(SIGLEC1):c.2921C>T(p.Ala974Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,613,248 control chromosomes in the GnomAD database, including 226,070 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.52 ( 21178 hom., cov: 33)

Exomes 𝑓: 0.53 ( 204892 hom. )

Consequence

SIGLEC1
ENST00000344754.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.804

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8835827E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 linkuse as main transcript	c.2921C>T	p.Ala974Val	missense_variant	12/22	ENST00000344754.6	NP_075556.1
SIGLEC1	NM_001367089.1 linkuse as main transcript	c.2921C>T	p.Ala974Val	missense_variant	11/20		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6 linkuse as main transcript	c.2921C>T	p.Ala974Val	missense_variant	12/22	1	NM_023068.4	ENSP00000341141	P2	Q9BZZ2-1
SIGLEC1	ENST00000707083.1 linkuse as main transcript	c.2921C>T	p.Ala974Val	missense_variant	11/20			ENSP00000516734	A2

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79503

AN:

152034

Hom.:

21165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.525

GnomAD3 exomes

AF:

0.575

AC:

144294

AN:

250744

Hom.:

42543

AF XY:

0.573

AC XY:

77727

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.684

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.761

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.619

Gnomad NFE exome

AF:

0.513

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.526

AC:

768539

AN:

1461096

Hom.:

204892

Cov.:

AF XY:

0.529

AC XY:

384603

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.675

Gnomad4 ASJ exome

AF:

0.526

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.626

Gnomad4 FIN exome

AF:

0.608

Gnomad4 NFE exome

AF:

0.504

Gnomad4 OTH exome

AF:

0.532

GnomAD4 genome

AF:

0.523

AC:

79551

AN:

152152

Hom.:

21178

Cov.:

AF XY:

0.534

AC XY:

39740

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.456

Gnomad4 AMR

AF:

0.599

Gnomad4 ASJ

AF:

0.520

Gnomad4 EAS

AF:

0.749

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.622

Gnomad4 NFE

AF:

0.509

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.518

Hom.:

38401

Bravo

AF:

0.516

TwinsUK

AF:

0.501

AC:

1857

ALSPAC

AF:

0.497

AC:

1915

ESP6500AA

AF:

0.445

AC:

1961

ESP6500EA

AF:

0.509

AC:

4380

ExAC

AF:

0.567

AC:

68859

Asia WGS

AF:

0.652

AC:

2271

AN:

3478

EpiCase

AF:

0.509

EpiControl

AF:

0.507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0000019

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

REVEL

Benign

0.056

Sift

Benign

0.12

Sift4G

Uncertain

0.028

Polyphen

0.20

Vest4

0.029

MPC

0.13

ClinPred

0.021

GERP RS

2.6

Varity_R

0.076

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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