rs9376090

Variant names:

• chr6-135090090-T-C
• rs9376090
• ENST00000529882.5:c.88+12838A>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+12838A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,116 control chromosomes in the GnomAD database, including 3,548 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 0.19 (3548 hom., cov: 32)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 77 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 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+12838A>G		intron	N/A	ENSP00000433030.1	E9PMN1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28511 AN: 151998 Hom.: 3548 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.187 AC: 28505 AN: 152116 Hom.: 3548 Cov.: 32 AF XY: 0.188 AC XY: 13955 AN XY: 74324

African (AFR) AF: 0.0432 AC: 1793 AN: 41548

American (AMR) AF: 0.159 AC: 2427 AN: 15274

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

East Asian (EAS) AF: 0.255 AC: 1320 AN: 5174

South Asian (SAS) AF: 0.110 AC: 530 AN: 4824

European-Finnish (FIN) AF: 0.345 AC: 3640 AN: 10548

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17459 AN: 67962

Other (OTH) AF: 0.155 AC: 328 AN: 2110

Alfa AF: 0.232 Hom.: 17312

Bravo AF: 0.170

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		0.075

Splicing

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

Other links and lift over

dbSNP: rs9376090; hg19: chr6-135411228;