Variant 8-132077903-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001145095.3(HHLA1):c.994G>A(p.Val332Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000803 in 1,551,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00085 ( 1 hom. )

Consequence

HHLA1
NM_001145095.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.43

Variant links:

Genes affected

HHLA1 (HGNC:4904): (HHLA1 neighbor of OC90) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

HHLA1 links:

ENSG00000258417 (HGNC:):

ENSG00000258417 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.013394803).

BP6

Variant 8-132077903-C-T is Benign according to our data. Variant chr8-132077903-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2271565.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHLA1	NM_001145095.3 linkuse as main transcript	c.994G>A	p.Val332Met	missense_variant	12/17	ENST00000414222.2	NP_001138567.1	C9JL84-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HHLA1	ENST00000414222.2 linkuse as main transcript	c.994G>A	p.Val332Met	missense_variant	12/17	5	NM_001145095.3	ENSP00000388322.1	C9JL84-1
ENSG00000258417	ENST00000262283.5 linkuse as main transcript	c.220G>A	p.Val74Met	missense_variant	2/18	5		ENSP00000262283.5	I6L893
HHLA1	ENST00000473291.1 linkuse as main transcript	n.1456G>A		non_coding_transcript_exon_variant	2/7	1
HHLA1	ENST00000673615.1 linkuse as main transcript	c.1102G>A	p.Val368Met	missense_variant	13/18			ENSP00000500443.1	A0A5F9ZHM0

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000436

AC:

AN:

156056

Hom.:

AF XY:

0.000387

AC XY:

AN XY:

82702

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.000351

Gnomad FIN exome

AF:

0.0000594

Gnomad NFE exome

AF:

0.000782

Gnomad OTH exome

AF:

0.000914

GnomAD4 exome

AF:

0.000849

AC:

1188

AN:

1399364

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

575

AN XY:

690192

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00104

Gnomad4 OTH exome

AF:

0.000466

GnomAD4 genome

AF:

0.000381

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000468

Hom.:

Bravo

AF:

0.000348

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.000280

AC:

Asia WGS

AF:

0.000866

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

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

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

0.071

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0050

DANN

Benign

0.84

DEOGEN2

Benign

0.00094

.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.40

N;N;N

REVEL

Benign

0.0040

Sift

Pathogenic

0.0

D;T;T

Sift4G

Uncertain

0.0080

D;T;T

Polyphen

0.011

.;B;.

Vest4

0.019

MVP

0.040

ClinPred

0.0046

GERP RS

-3.2

Varity_R

0.013

gMVP

0.085

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over