6-134966324-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006620.4(HBS1L):c.2043+5T>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,604,808 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

HBS1L
NM_006620.4 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.003293

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.302

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-134966324-A-C is Benign according to our data. Variant chr6-134966324-A-C is described in ClinVar as [Benign]. Clinvar id is 778253.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0055 (837/152286) while in subpopulation AFR AF= 0.0169 (704/41568). AF 95% confidence interval is 0.0159. There are 8 homozygotes in gnomad4. There are 390 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HBS1L	NM_006620.4 linkuse as main transcript	c.2043+5T>G	splice_donor_5th_base_variant, intron_variant	ENST00000367837.10
HBS1L	NM_001145158.2 linkuse as main transcript	c.1917+5T>G	splice_donor_5th_base_variant, intron_variant
HBS1L	NM_001363686.2 linkuse as main transcript	c.1551+5T>G	splice_donor_5th_base_variant, intron_variant
HBS1L	XM_047418093.1 linkuse as main transcript		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBS1L	ENST00000367837.10 linkuse as main transcript	c.2043+5T>G		splice_donor_5th_base_variant, intron_variant		1	NM_006620.4	P1	Q9Y450-1

Frequencies

GnomAD3 genomes

AF:

0.00550

AC:

837

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00219

AC:

533

AN:

243084

Hom.:

AF XY:

0.00183

AC XY:

240

AN XY:

131258

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000140

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000513

Gnomad OTH exome

AF:

0.00237

GnomAD4 exome

AF:

0.00102

AC:

1482

AN:

1452522

Hom.:

Cov.:

AF XY:

0.000961

AC XY:

694

AN XY:

722260

show subpopulations

Gnomad4 AFR exome

AF:

0.0190

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000294

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00550

AC:

837

AN:

152286

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

390

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.00644

Asia WGS

AF:

0.00173

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

5.0

Dann

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0033

dbscSNV1_RF

Benign

0.070

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