6-135054094-C-T

Position:

• chr6-135054094-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006620.4(HBS1L):​c.43+555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,048 control chromosomes in the GnomAD database, including 19,197 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 0.50 (19197 hom., cov: 33)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HBS1L	NM_006620.4	c.43+555G>A		intron_variant		ENST00000367837.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBS1L	ENST00000367837.10	c.43+555G>A		intron_variant		1	NM_006620.4	P1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76119 AN: 151930 Hom.: 19166 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.501 AC: 76191 AN: 152048 Hom.: 19197 Cov.: 33 AF XY: 0.505 AC XY: 37504 AN XY: 74308

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.482

Alfa AF: 0.510 Hom.: 4893

Bravo AF: 0.492

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2150681; hg19: chr6-135375232; COSMIC: COSV59020047; COSMIC: COSV59020047;