rs9373124

Positions:

• chr6-135102071-T-C

Variant summary

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

The ENST00000529882.5(HBS1L):​c.88+857A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,096 control chromosomes in the GnomAD database, including 9,081 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 0.33 (9081 hom., cov: 32)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBS1L	ENST00000529882.5	c.88+857A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49655 AN: 151978 Hom.: 9052 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.327 AC: 49734 AN: 152096 Hom.: 9081 Cov.: 32 AF XY: 0.322 AC XY: 23965 AN XY: 74342

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.287

Alfa AF: 0.281 Hom.: 6771

Bravo AF: 0.332

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9373124; hg19: chr6-135423209;