6-135102071-T-C

Variant names:

• chr6-135102071-T-C
• rs9373124
• ENST00000529882.5:c.88+857A>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+857A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,096 control chromosomes in the GnomAD database, including 9,081 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 0.33 (9081 hom., cov: 32)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979
• Publications: 40 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 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.88+857A>G		intron	N/A	ENSP00000433030.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49655 AN: 151978 Hom.: 9052 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.327 AC: 49734 AN: 152096 Hom.: 9081 Cov.: 32 AF XY: 0.322 AC XY: 23965 AN XY: 74342

African (AFR) AF: 0.481 AC: 19940 AN: 41458

American (AMR) AF: 0.253 AC: 3869 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1456 AN: 5178

South Asian (SAS) AF: 0.113 AC: 545 AN: 4820

European-Finnish (FIN) AF: 0.348 AC: 3685 AN: 10582

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18505 AN: 67976

Other (OTH) AF: 0.287 AC: 607 AN: 2114

Alfa AF: 0.291 Hom.: 19594

Bravo AF: 0.332

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.48
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs9373124; hg19: chr6-135423209;