Genetic Variant SIGLEC11:p.Val581Ile (chr19-49952305-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_052884.3(SIGLEC11):c.1741G>A(p.Val581Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,612,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SIGLEC11
NM_052884.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.05

Publications

11 publications found

Variant links:

Genes affected

SIGLEC11 (HGNC:15622): (sialic acid binding Ig like lectin 11) This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. This family member mediates anti-inflammatory and immunosuppressive signaling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SIGLEC11 links:

ENSG00000269179 (HGNC:):

ENSG00000269179 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01877141).

BP6

Variant 19-49952305-C-T is Benign according to our data. Variant chr19-49952305-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2382108.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052884.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC11	NM_052884.3	MANE Select	c.1741G>A	p.Val581Ile	missense	Exon 9 of 11	NP_443116.2	Q96RL6-1
	SIGLEC11	NM_001135163.1		c.1453G>A	p.Val485Ile	missense	Exon 8 of 10	NP_001128635.1	Q96RL6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIGLEC11	ENST00000447370.6	TSL:1 MANE Select	c.1741G>A	p.Val581Ile	missense	Exon 9 of 11	ENSP00000412361.2	Q96RL6-1
SIGLEC11	ENST00000426971.2	TSL:1	c.1453G>A	p.Val485Ile	missense	Exon 8 of 10	ENSP00000398891.2	Q96RL6-2
ENSG00000269179	ENST00000451973.1	TSL:2	n.110-333G>A		intron	N/A	ENSP00000391489.1	H7BZU6

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.0000844

AC:

AN:

248910

AF XY:

0.0000741

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000160

AC:

234

AN:

1460366

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

726588

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000189

AC:

210

AN:

1111896

Other (OTH)

AF:

0.000182

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000164

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41576

American (AMR)

AF:

0.000196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68014

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000214

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0050

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0024

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.16

M_CAP

Benign

0.0031

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

-2.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.48

REVEL

Benign

0.040

Sift

Benign

0.97

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.063

MutPred

0.40

Loss of sheet (P = 0.1158)

MVP

0.31

MPC

0.011

ClinPred

0.014

GERP RS

-6.3

Varity_R

0.013

gMVP

0.080

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over