Genetic Variant HBS1L:c.89-4424A>C (chr6-135055071-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000529882.5(HBS1L):c.89-4424A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 418,216 control chromosomes in the GnomAD database, including 24,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.31 ( 7870 hom., cov: 33)

Exomes 𝑓: 0.35 ( 16941 hom. )

Consequence

HBS1L
ENST00000529882.5 intron

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -1.27

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:

ENSG00000232876 (HGNC:):

ENSG00000232876 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBS1L	NM_006620.4 link	c.-380A>C		upstream_gene_variant		ENST00000367837.10	NP_006611.1	Q9Y450-1D9YZV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10 link	c.-380A>C		upstream_gene_variant		1	NM_006620.4	ENSP00000356811.5		Q9Y450-1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47587

AN:

152102

Hom.:

7863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.285

GnomAD4 exome

AF:

0.355

AC:

94332

AN:

265996

Hom.:

16941

Cov.:

AF XY:

0.354

AC XY:

48037

AN XY:

135536

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.419

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.313

AC:

47615

AN:

152220

Hom.:

7870

Cov.:

AF XY:

0.310

AC XY:

23106

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.432

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.281

Hom.:

1335

Bravo

AF:

0.297

Asia WGS

AF:

0.301

AC:

1049

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.1

DANN

Benign

0.71

Splicing

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