rs1547247

Variant names:

• chr6-135069698-G-A
• rs1547247
• ENST00000529882.5:c.89-19051C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000529882.5	c.89-19051C>T		intron_variant	Intron 1 of 4	4		ENSP00000433030.1

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

African (AFR) AF: 0.0651 AC: 2703 AN: 41544

American (AMR) AF: 0.179 AC: 2742 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3468

East Asian (EAS) AF: 0.128 AC: 662 AN: 5180

South Asian (SAS) AF: 0.111 AC: 536 AN: 4830

European-Finnish (FIN) AF: 0.362 AC: 3824 AN: 10554

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20813 AN: 67972

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.274 Hom.: 10645

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
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs1547247; hg19: chr6-135390836;