rs9399137

Variant names:

• chr6-135097880-T-C
• rs9399137
• ENST00000529882.5:c.88+5048A>G

Variant summary

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

The ENST00000529882.5(HBS1L):​c.88+5048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,414 control chromosomes in the GnomAD database, including 3,659 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 0.20 (3659 hom., cov: 32)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 156 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=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000529882.5	TSL:4	c.88+5048A>G		intron	N/A	ENSP00000433030.1	E9PMN1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29748 AN: 151300 Hom.: 3657 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.197 AC: 29754 AN: 151414 Hom.: 3659 Cov.: 32 AF XY: 0.197 AC XY: 14548 AN XY: 74014

African (AFR) AF: 0.0680 AC: 2778 AN: 40842

American (AMR) AF: 0.162 AC: 2470 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1319 AN: 5174

South Asian (SAS) AF: 0.109 AC: 527 AN: 4826

European-Finnish (FIN) AF: 0.348 AC: 3669 AN: 10556

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17634 AN: 67956

Other (OTH) AF: 0.163 AC: 343 AN: 2108

Alfa AF: 0.234 Hom.: 11700

Bravo AF: 0.179

Asia WGS AF: 0.151 AC: 522 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.041

Splicing

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

Other links and lift over

dbSNP: rs9399137; hg19: chr6-135419018;