6-135103065-G-T

Variant names:

• chr6-135103065-G-T
• rs6930223
• ENST00000529882.5:c.-50C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000529882.5(HBS1L):​c.-50C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 205,412 control chromosomes in the GnomAD database, including 33,561 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 0.58 (26356 hom., cov: 30)
  • Exomes 𝑓: 0.50 (7205 hom.)
• Consequence: HBS1L ENST00000529882.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• Publications: 11 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529882.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000529882.5	TSL:4	c.-50C>A		upstream_gene	N/A	ENSP00000433030.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87504 AN: 151462 Hom.: 26299 Cov.: 30

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.563

GnomAD2 exomes AF: 0.531 AC: 2958 AN: 5568 AF XY: 0.529

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.539

Gnomad ASJ exome AF: 0.392

Gnomad EAS exome AF: 0.663

Gnomad FIN exome AF: 0.649

Gnomad NFE exome AF: 0.530

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.496 AC: 26702 AN: 53832 Hom.: 7205 Cov.: 0 AF XY: 0.496 AC XY: 15883 AN XY: 32044

African (AFR) AF: 0.739 AC: 278 AN: 376

American (AMR) AF: 0.532 AC: 1040 AN: 1956

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 373 AN: 1020

East Asian (EAS) AF: 0.615 AC: 406 AN: 660

South Asian (SAS) AF: 0.494 AC: 6584 AN: 13338

European-Finnish (FIN) AF: 0.635 AC: 1667 AN: 2624

Middle Eastern (MID) AF: 0.399 AC: 719 AN: 1804

European-Non Finnish (NFE) AF: 0.486 AC: 14402 AN: 29610

Other (OTH) AF: 0.505 AC: 1233 AN: 2444

GnomAD4 genome AF: 0.578 AC: 87621 AN: 151580 Hom.: 26356 Cov.: 30 AF XY: 0.580 AC XY: 42932 AN XY: 74058

African (AFR) AF: 0.739 AC: 30550 AN: 41350

American (AMR) AF: 0.506 AC: 7720 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1437 AN: 3466

East Asian (EAS) AF: 0.597 AC: 3058 AN: 5126

South Asian (SAS) AF: 0.496 AC: 2391 AN: 4816

European-Finnish (FIN) AF: 0.652 AC: 6820 AN: 10464

Middle Eastern (MID) AF: 0.455 AC: 132 AN: 290

European-Non Finnish (NFE) AF: 0.501 AC: 33961 AN: 67810

Other (OTH) AF: 0.566 AC: 1195 AN: 2110

Alfa AF: 0.520 Hom.: 25035

Bravo AF: 0.579

Asia WGS AF: 0.605 AC: 2098 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		0.23
PromoterAI		-0.042	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6930223; hg19: chr6-135424203; COSMIC: COSV73231425;