6-135054094-C-T

Variant names:

• chr6-135054094-C-T
• rs2150681
• NM_006620.4:c.43+555G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.84).
• 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 rank	MANE	Protein	UniProt
HBS1L	NM_006620.4	c.43+555G>A		intron_variant	Intron 1 of 17	ENST00000367837.10	NP_006611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10	c.43+555G>A		intron_variant	Intron 1 of 17	1	NM_006620.4	ENSP00000356811.5

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

African (AFR) AF: 0.489 AC: 20255 AN: 41460

American (AMR) AF: 0.494 AC: 7540 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1637 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2752 AN: 5178

South Asian (SAS) AF: 0.564 AC: 2720 AN: 4822

European-Finnish (FIN) AF: 0.585 AC: 6187 AN: 10570

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33642 AN: 67962

Other (OTH) AF: 0.482 AC: 1018 AN: 2112

Alfa AF: 0.503 Hom.: 5459

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
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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