rs7775698

Variant names:

• chr6-135097497-C-T
• rs7775698
• ENST00000529882.5:c.88+5431G>A

Variant summary

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

The ENST00000529882.5(HBS1L):​c.88+5431G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 100,758 control chromosomes in the GnomAD database, including 508 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 0.066 (508 hom., cov: 26)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 52 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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000529882.5	TSL:4	c.88+5431G>A		intron	N/A	ENSP00000433030.1

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 6646 AN: 100646 Hom.: 505 Cov.: 26

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000342

Gnomad SAS AF: 0.00182

Gnomad FIN AF: 0.000672

Gnomad MID AF: 0.0198

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0509

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

GnomAD4 genome AF: 0.0661 AC: 6662 AN: 100758 Hom.: 508 Cov.: 26 AF XY: 0.0640 AC XY: 3156 AN XY: 49304

African (AFR) AF: 0.169 AC: 6231 AN: 36914

American (AMR) AF: 0.0258 AC: 279 AN: 10826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2060

East Asian (EAS) AF: 0.000343 AC: 1 AN: 2912

South Asian (SAS) AF: 0.00156 AC: 6 AN: 3834

European-Finnish (FIN) AF: 0.000672 AC: 3 AN: 4464

Middle Eastern (MID) AF: 0.0208 AC: 4 AN: 192

European-Non Finnish (NFE) AF: 0.00160 AC: 60 AN: 37394

Other (OTH) AF: 0.0516 AC: 78 AN: 1512

Alfa AF: 0.248 Hom.: 18673

Bravo AF: 0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs7775698; hg19: chr6-135418635;