Variant 6-135002834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006620.4(HBS1L):c.439G>A(p.Val147Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00854 in 1,610,010 control chromosomes in the GnomAD database, including 90 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0089 ( 86 hom. )

Consequence

HBS1L
NM_006620.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.925

Variant links:

Genes affected

HBS1L (HGNC:4834): (HBS1 like translational GTPase) This gene encodes a member of the GTP-binding elongation factor family. It is expressed in multiple tissues with the highest expression in heart and skeletal muscle. The intergenic region of this gene and the MYB gene has been identified to be a quantitative trait locus (QTL) controlling fetal hemoglobin level, and this region influnces erythrocyte, platelet, and monocyte counts as well as erythrocyte volume and hemoglobin content. DNA polymorphisms at this region associate with fetal hemoglobin levels and pain crises in sickle cell disease. A single nucleotide polymorphism in exon 1 of this gene is significantly associated with severity in beta-thalassemia/Hemoglobin E. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, May 2009]

HBS1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033268034).

BP6

Variant 6-135002834-C-T is Benign according to our data. Variant chr6-135002834-C-T is described in ClinVar as [Benign]. Clinvar id is 777171.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBS1L	NM_006620.4 link	c.439G>A	p.Val147Ile	missense_variant	5/18	ENST00000367837.10	NP_006611.1	Q9Y450-1D9YZV0
HBS1L	NM_001145158.2 link	c.313G>A	p.Val105Ile	missense_variant	4/17		NP_001138630.1	Q9Y450-4
HBS1L	XM_047418093.1 link	c.439G>A	p.Val147Ile	missense_variant	5/16		XP_047274049.1
HBS1L	NM_001363686.2 link	c.-54G>A		5_prime_UTR_variant	6/19		NP_001350615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10 link	c.439G>A	p.Val147Ile	missense_variant	5/18	1	NM_006620.4	ENSP00000356811.5		Q9Y450-1

Frequencies

GnomAD3 genomes

AF:

0.00547

AC:

832

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00539

AC:

1352

AN:

250820

Hom.:

AF XY:

0.00541

AC XY:

734

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00426

GnomAD4 exome

AF:

0.00886

AC:

12922

AN:

1457772

Hom.:

Cov.:

AF XY:

0.00857

AC XY:

6215

AN XY:

725428

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000604

Gnomad4 FIN exome

AF:

0.00266

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00538

GnomAD4 genome

AF:

0.00547

AC:

832

AN:

152238

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00898

Hom.:

Bravo

AF:

0.00523

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00560

AC:

680

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00816

EpiControl

AF:

0.00979

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.54

DANN

Benign

0.84

DEOGEN2

Benign

0.056

T;T;.;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.68

T;T;T;T;T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0033

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.32

N;N;N;N;N;N

REVEL

Benign

0.090

Sift

Benign

0.29

T;T;T;T;T;T

Sift4G

Benign

0.51

T;T;T;T;.;.

Polyphen

0.0

B;.;B;.;.;.

Vest4

0.052

MVP

0.30

MPC

0.13

ClinPred

0.00078

GERP RS

-7.0

Varity_R

0.022

gMVP

0.074

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over