6-135093866-C-T

Position:

• chr6-135093866-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000529882.5(HBS1L):​c.88+9062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,050 control chromosomes in the GnomAD database, including 30,429 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 0.62 (30429 hom., cov: 32)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000529882.5	c.88+9062G>A		intron_variant		4		ENSP00000433030

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93771 AN: 151930 Hom.: 30366 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.618 AC: 93892 AN: 152050 Hom.: 30429 Cov.: 32 AF XY: 0.621 AC XY: 46123 AN XY: 74324

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.578

Alfa AF: 0.519 Hom.: 40711

Bravo AF: 0.618

Asia WGS AF: 0.654 AC: 2273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7745098; hg19: chr6-135415004;