6-135103041-C-G

Variant names:

• chr6-135103041-C-G
• rs35959442
• ENST00000529882.5:c.-26G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 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.-26G>C		5_prime_UTR	Exon 1 of 5	ENSP00000433030.1

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

GnomAD2 exomes AF: 0.235 AC: 6037 AN: 25652 AF XY: 0.227

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 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

African (AFR) AF: 0.329 AC: 663 AN: 2014

American (AMR) AF: 0.206 AC: 1252 AN: 6068

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 933 AN: 4192

East Asian (EAS) AF: 0.290 AC: 909 AN: 3136

South Asian (SAS) AF: 0.116 AC: 4531 AN: 38958

European-Finnish (FIN) AF: 0.347 AC: 2711 AN: 7804

Middle Eastern (MID) AF: 0.193 AC: 435 AN: 2254

European-Non Finnish (NFE) AF: 0.267 AC: 26738 AN: 100112

Other (OTH) AF: 0.262 AC: 2142 AN: 8174

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

African (AFR) AF: 0.365 AC: 15106 AN: 41378

American (AMR) AF: 0.236 AC: 3606 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1444 AN: 5162

South Asian (SAS) AF: 0.112 AC: 540 AN: 4816

European-Finnish (FIN) AF: 0.347 AC: 3650 AN: 10520

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18312 AN: 67946

Other (OTH) AF: 0.257 AC: 542 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.62
PhyloP100		0.097
PromoterAI		0.0022	Neutral

Splicing

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

Other links and lift over

dbSNP: rs35959442; hg19: chr6-135424179;