Genetic Variant HBS1L:c.43+555G>A (chr6-135054094-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006620.4(HBS1L):c.43+555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,048 control chromosomes in the GnomAD database, including 19,197 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19197 hom., cov: 33)

Consequence

HBS1L
NM_006620.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

16 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006620.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HBS1L	NM_006620.4	MANE Select	c.43+555G>A	intron	N/A	NP_006611.1	Q9Y450-1
HBS1L	NM_001145158.2		c.43+555G>A	intron	N/A	NP_001138630.1	Q9Y450-4
HBS1L	NM_001145207.2		c.43+555G>A	intron	N/A	NP_001138679.1	Q9Y450-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HBS1L	ENST00000367837.10	TSL:1 MANE Select	c.43+555G>A	intron	N/A	ENSP00000356811.5	Q9Y450-1
HBS1L	ENST00000367822.9	TSL:1	c.43+555G>A	intron	N/A	ENSP00000356796.5	Q9Y450-2
HBS1L	ENST00000949311.1		c.43+555G>A	intron	N/A	ENSP00000619370.1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76119

AN:

151930

Hom.:

19166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.564

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.501

AC:

76191

AN:

152048

Hom.:

19197

Cov.:

AF XY:

0.505

AC XY:

37504

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.489

AC:

20255

AN:

41460

American (AMR)

AF:

0.494

AC:

7540

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

1637

AN:

3468

East Asian (EAS)

AF:

0.531

AC:

2752

AN:

5178

South Asian (SAS)

AF:

0.564

AC:

2720

AN:

4822

European-Finnish (FIN)

AF:

0.585

AC:

6187

AN:

10570

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.495

AC:

33642

AN:

67962

Other (OTH)

AF:

0.482

AC:

1018

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1971

3942

5913

7884

9855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.503

Hom.:

5459

Bravo

AF:

0.492

Asia WGS

AF:

0.566

AC:

1969

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.9

(source)

DANN

Benign

0.47

PhyloP100

-0.066

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over