19-49952305-C-T

Variant names:

• chr19-49952305-C-T
• rs140702198
• NM_052884.3:c.1741G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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. 16/21 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

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]

ENSG00000269179 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 id is 2382108.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLEC11	NM_052884.3	c.1741G>A	p.Val581Ile	missense_variant	Exon 9 of 11	ENST00000447370.6	NP_443116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLEC11	ENST00000447370.6	c.1741G>A	p.Val581Ile	missense_variant	Exon 9 of 11	1	NM_052884.3	ENSP00000412361.2
SIGLEC11	ENST00000426971.2	c.1453G>A	p.Val485Ile	missense_variant	Exon 8 of 10	1		ENSP00000398891.2
ENSG00000269179	ENST00000451973.1	n.110-333G>A		intron_variant	Intron 1 of 2	2		ENSP00000391489.1
SIGLEC11	ENST00000426296.1	n.176-333G>A		intron_variant	Intron 1 of 2	2		ENSP00000407387.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152188 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.0000844 AC: 21 AN: 248910 Hom.: 0 AF XY: 0.0000741 AC XY: 10 AN XY: 134942

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 SAS exome AF: 0.00

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.: 0 Cov.: 31 AF XY: 0.000147 AC XY: 107 AN XY: 726588

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000189

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74470

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.0000214 Hom.: 1

Bravo AF: 0.000159

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 06, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0050
DANN	Benign	0.64
DEOGEN2	Benign	0.0024	T;.
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.019	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.48	N;.
REVEL	Benign	0.040
Sift	Benign	0.97	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.063
MutPred		0.40		Loss of sheet (P = 0.1158);.;
MVP		0.31
MPC		0.011
ClinPred		0.014	T
GERP RS		-6.3
Varity_R		0.013
gMVP		0.080

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

Other links and lift over

dbSNP: rs140702198; hg19: chr19-50455562; COSMIC: COSV68567498; COSMIC: COSV68567498;