Variant 6-135002823-C-G 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.450G>C(p.Gln150His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,612,204 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

HBS1L
NM_006620.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43

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=0.0039607882).

BP6

Variant 6-135002823-C-G is Benign according to our data. Variant chr6-135002823-C-G is described in ClinVar as [Benign]. Clinvar id is 720121.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 linkuse as main transcript	c.450G>C	p.Gln150His	missense_variant	5/18	ENST00000367837.10	NP_006611.1	Q9Y450-1D9YZV0
HBS1L	NM_001145158.2 linkuse as main transcript	c.324G>C	p.Gln108His	missense_variant	4/17		NP_001138630.1	Q9Y450-4
HBS1L	XM_047418093.1 linkuse as main transcript	c.450G>C	p.Gln150His	missense_variant	5/16		XP_047274049.1
HBS1L	NM_001363686.2 linkuse as main transcript	c.-43G>C		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 linkuse as main transcript	c.450G>C	p.Gln150His	missense_variant	5/18	1	NM_006620.4	ENSP00000356811.5		Q9Y450-1

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

361

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00812

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000705

AC:

177

AN:

251052

Hom.:

AF XY:

0.000568

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00930

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000201

AC:

293

AN:

1460064

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

121

AN XY:

726414

show subpopulations

Gnomad4 AFR exome

AF:

0.00613

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000746

GnomAD4 genome

AF:

0.00236

AC:

359

AN:

152140

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

173

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00805

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000922

Hom.:

Bravo

AF:

0.00277

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000939

AC:

114

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

May 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

T;T;.;T;T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

T;T;T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.8

L;.;.;.;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.11

T;D;T;T;T;D

Sift4G

Benign

0.12

T;T;T;T;.;.

Polyphen

0.39

B;.;P;.;.;.

Vest4

0.19

MutPred

0.051

Loss of methylation at K145 (P = 0.0903);.;.;.;.;.;

MVP

0.69

MPC

0.26

ClinPred

0.011

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.26

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