dbSNP rs35959442: HBS1L:c.-26G>C (chr6-135103041-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000529882.5(HBS1L):c.-26G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 324,586 control chromosomes in the GnomAD database, including 12,377 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 0.29 ( 6867 hom., cov: 31)

Exomes 𝑓: 0.23 ( 5510 hom. )

Consequence

HBS1L
ENST00000529882.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0970

Publications

24 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000529882.5 link	c.-26G>C		5_prime_UTR_variant	Exon 1 of 5	4		ENSP00000433030.1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44218

AN:

151758

Hom.:

6847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.255

GnomAD2 exomes

AF:

0.235

AC:

6037

AN:

25652

AF XY:

0.227

show subpopulations

Gnomad AFR exome

AF:

0.366

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.233

AC:

40314

AN:

172712

Hom.:

5510

Cov.:

AF XY:

0.219

AC XY:

22427

AN XY:

102310

show subpopulations

African (AFR)

AF:

0.329

AC:

663

AN:

2014

American (AMR)

AF:

0.206

AC:

1252

AN:

6068

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

933

AN:

4192

East Asian (EAS)

AF:

0.290

AC:

909

AN:

3136

South Asian (SAS)

AF:

0.116

AC:

4531

AN:

38958

European-Finnish (FIN)

AF:

0.347

AC:

2711

AN:

7804

Middle Eastern (MID)

AF:

0.193

AC:

435

AN:

2254

European-Non Finnish (NFE)

AF:

0.267

AC:

26738

AN:

100112

Other (OTH)

AF:

0.262

AC:

2142

AN:

8174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1305

2610

3916

5221

6526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.292

AC:

44273

AN:

151874

Hom.:

6867

Cov.:

AF XY:

0.289

AC XY:

21424

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.365

AC:

15106

AN:

41378

American (AMR)

AF:

0.236

AC:

3606

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

830

AN:

3468

East Asian (EAS)

AF:

0.280

AC:

1444

AN:

5162

South Asian (SAS)

AF:

0.112

AC:

540

AN:

4816

European-Finnish (FIN)

AF:

0.347

AC:

3650

AN:

10520

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.270

AC:

18312

AN:

67946

Other (OTH)

AF:

0.257

AC:

542

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1548

3097

4645

6194

7742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.157

Hom.:

311

Bravo

AF:

0.292

Asia WGS

AF:

0.206

AC:

716

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

8.3

(source)

DANN

Benign

0.62

PhyloP100

0.097

PromoterAI

0.0022

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over