rs1547247

chr6-135069698-G-A

Variant summary

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

The ENST00000529882.5(HBS1L):c.89-19051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,152 control chromosomes in the GnomAD database, including 4,558 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 0.22 (4558 hom., cov: 32)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 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.89-19051C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32923 AN: 152034 Hom.: 4556 Cov.: 32

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.216 AC: 32922 AN: 152152 Hom.: 4558 Cov.: 32 AF XY: 0.214 AC XY: 15935 AN XY: 74352

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.188

Alfa AF: 0.280 Hom.: 8709

Bravo AF: 0.200

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.1
Dann	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1547247; hg19: chr6-135390836;