3-108353477-G-A

Variant names:

Variant summary

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

The NM_001282556.2(HHLA2):c.115G>A(p.Val39Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 1,602,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

HHLA2
NM_001282556.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.584

Publications

0 publications found

Variant links:

Genes affected

HHLA2 (HGNC:4905): (HHLA2 member of B7 family) This gene encodes a protein ligand found on the surface of monocytes. The encoded protein is thought to regulate cell-mediated immunity by binding to a receptor on T lymphocytes and inhibiting the proliferation of these cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

HHLA2 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=0.03918621).

BP6

Variant 3-108353477-G-A is Benign according to our data. Variant chr3-108353477-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2344527.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHLA2	NM_001282556.2 link	c.115G>A	p.Val39Ile	missense_variant	Exon 4 of 10	ENST00000467761.6	NP_001269485.1	Q9UM44-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHLA2	ENST00000467761.6 link	c.115G>A	p.Val39Ile	missense_variant	Exon 4 of 10	5	NM_001282556.2	ENSP00000419207.1		Q9UM44-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000120

AC:

AN:

232934

AF XY:

0.0000793

show subpopulations

Gnomad AFR exome

AF:

0.0000703

Gnomad AMR exome

AF:

0.000771

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000358

AC:

AN:

1450882

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

720696

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33364

American (AMR)

AF:

0.000653

AC:

AN:

42890

Ashkenazi Jewish (ASJ)

AF:

0.0000387

AC:

AN:

25818

East Asian (EAS)

AF:

0.00

AC:

AN:

39392

South Asian (SAS)

AF:

0.0000354

AC:

AN:

84644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000181

AC:

AN:

1106202

Other (OTH)

AF:

0.00

AC:

AN:

60054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41424

American (AMR)

AF:

0.000197

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000829

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 10, 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

0.082

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.85

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.013

T;T;.;T;.;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.55

T;T;T;T;T;T;.;.;.

M_CAP

Benign

0.0080

MetaRNN

Benign

0.039

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.;.;.;.;L;L;L

PhyloP100

0.58

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.44

.;N;N;N;N;N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.13

.;T;T;T;T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T;T;T;T;T

Polyphen

0.031

B;.;.;B;.;.;B;B;B

Vest4

0.093

MutPred

0.52

Loss of catalytic residue at V39 (P = 0.0824);.;Loss of catalytic residue at V39 (P = 0.0824);Loss of catalytic residue at V39 (P = 0.0824);Loss of catalytic residue at V39 (P = 0.0824);Loss of catalytic residue at V39 (P = 0.0824);Loss of catalytic residue at V39 (P = 0.0824);Loss of catalytic residue at V39 (P = 0.0824);Loss of catalytic residue at V39 (P = 0.0824);

MVP

0.12

MPC

0.18

ClinPred

0.029

GERP RS

0.18

PromoterAI

-0.0097

Neutral

(source)

Varity_R

0.029

gMVP

0.11

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

3-108353477-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over