chr6-135098550-T-C

Variant names:

• chr6-135098550-T-C
• rs9402685
• ENST00000529882.5:c.88+4378A>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+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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5204 hom., cov: 31)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 21 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=-0.92).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000529882.5	c.88+4378A>G		intron_variant	Intron 1 of 4	4		ENSP00000433030.1

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

African (AFR) AF: 0.274 AC: 11361 AN: 41440

American (AMR) AF: 0.185 AC: 2826 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1326 AN: 5176

South Asian (SAS) AF: 0.111 AC: 538 AN: 4830

European-Finnish (FIN) AF: 0.347 AC: 3659 AN: 10530

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17741 AN: 67940

Other (OTH) AF: 0.213 AC: 450 AN: 2110

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
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs9402685; hg19: chr6-135419688;