rs35959442

Positions:

• chr6-135103041-C-G
• chr6-135103041-C-T

Variant summary

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

The ENST00000529882.5(HBS1L):​c.-26G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 324,586 control chromosomes in the GnomAD database, including 12,377 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 0.29 (6867 hom., cov: 31)
  • Exomes 𝑓: 0.23 (5510 hom.)
• Consequence: HBS1L ENST00000529882.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 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.-26G>C		5_prime_UTR_variant	1/5	4		ENSP00000433030

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44218 AN: 151758 Hom.: 6847 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.255

GnomAD3 exomes AF: 0.235 AC: 6037 AN: 25652 Hom.: 828 AF XY: 0.227 AC XY: 3468 AN XY: 15278

Gnomad AFR exome AF: 0.366

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.304

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.233 AC: 40314 AN: 172712 Hom.: 5510 Cov.: 0 AF XY: 0.219 AC XY: 22427 AN XY: 102310

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.292 AC: 44273 AN: 151874 Hom.: 6867 Cov.: 31 AF XY: 0.289 AC XY: 21424 AN XY: 74228

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.257

Alfa AF: 0.157 Hom.: 311

Bravo AF: 0.292

Asia WGS AF: 0.206 AC: 716 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35959442; hg19: chr6-135424179;