rs9402685

Positions:

• chr6-135098550-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000529882.5(HBS1L):​c.88+4378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,960 control chromosomes in the GnomAD database, including 5,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.26 (5204 hom., cov: 31)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-135098550-T-C is Benign according to our data. Variant chr6-135098550-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000529882.5	c.88+4378A>G		intron_variant		4		ENSP00000433030

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38906 AN: 151844 Hom.: 5199 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.256 AC: 38937 AN: 151960 Hom.: 5204 Cov.: 31 AF XY: 0.254 AC XY: 18847 AN XY: 74266

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.213

Alfa AF: 0.263 Hom.: 678

Bravo AF: 0.249

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9402685; hg19: chr6-135419688;