dbSNP rs625372: SIGLEC1:p.Lys239Arg (chr20-3704082-T-C) – 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.716A>G(p.Lys239Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,611,512 control chromosomes in the GnomAD database, including 332,206 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.63 ( 30205 hom., cov: 31)

Exomes 𝑓: 0.64 ( 302001 hom. )

Consequence

SIGLEC1
NM_023068.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0130

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=2.3265331E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC1	NM_023068.4 link	c.716A>G	p.Lys239Arg	missense_variant	Exon 5 of 22	ENST00000344754.6	NP_075556.1	Q9BZZ2-1
SIGLEC1	NM_001367089.1 link	c.716A>G	p.Lys239Arg	missense_variant	Exon 4 of 20		NP_001354018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC1	ENST00000344754.6 link	c.716A>G	p.Lys239Arg	missense_variant	Exon 5 of 22	1	NM_023068.4	ENSP00000341141.4		Q9BZZ2-1
SIGLEC1	ENST00000707083.1 link	c.716A>G	p.Lys239Arg	missense_variant	Exon 4 of 20			ENSP00000516734.1		Q9BZZ2-3

Frequencies

GnomAD3 genomes

AF:

0.629

AC:

95440

AN:

151654

Hom.:

30169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.749

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.623

GnomAD3 exomes

AF:

0.644

AC:

160335

AN:

248878

Hom.:

52041

AF XY:

0.647

AC XY:

87094

AN XY:

134716

show subpopulations

Gnomad AFR exome

AF:

0.567

Gnomad AMR exome

AF:

0.593

Gnomad ASJ exome

AF:

0.637

Gnomad EAS exome

AF:

0.669

Gnomad SAS exome

AF:

0.614

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.656

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.642

AC:

936935

AN:

1459740

Hom.:

302001

Cov.:

AF XY:

0.642

AC XY:

466219

AN XY:

725982

show subpopulations

Gnomad4 AFR exome

AF:

0.570

Gnomad4 AMR exome

AF:

0.598

Gnomad4 ASJ exome

AF:

0.638

Gnomad4 EAS exome

AF:

0.683

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.741

Gnomad4 NFE exome

AF:

0.642

Gnomad4 OTH exome

AF:

0.644

GnomAD4 genome

AF:

0.629

AC:

95517

AN:

151772

Hom.:

30205

Cov.:

AF XY:

0.637

AC XY:

47234

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.671

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.749

Gnomad4 NFE

AF:

0.649

Gnomad4 OTH

AF:

0.618

Alfa

AF:

0.642

Hom.:

63416

Bravo

AF:

0.613

TwinsUK

AF:

0.639

AC:

2369

ALSPAC

AF:

0.641

AC:

2470

ESP6500AA

AF:

0.561

AC:

2472

ESP6500EA

AF:

0.644

AC:

5542

ExAC

AF:

0.644

AC:

78231

Asia WGS

AF:

0.629

AC:

2190

AN:

3478

EpiCase

AF:

0.643

EpiControl

AF:

0.645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.4

DANN

Benign

0.97

DEOGEN2

Benign

0.13

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.48

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.65

REVEL

Benign

0.061

Sift

Benign

0.21

Sift4G

Benign

0.59

Polyphen

0.034

Vest4

0.029

MPC

0.12

ClinPred

0.0051

GERP RS

-3.2

Varity_R

0.080

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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