6-135053230-C-G

Variant names:

• chr6-135053230-C-G
• rs7741515
• NM_006620.4:c.43+1419G>C

Variant summary

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

The NM_006620.4(HBS1L):​c.43+1419G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,932 control chromosomes in the GnomAD database, including 16,862 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 0.47 (16862 hom., cov: 31)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-0.79).
• 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+1419G>C		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+1419G>C		intron_variant	Intron 1 of 17	1	NM_006620.4	ENSP00000356811.5

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70807 AN: 151814 Hom.: 16843 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.466 AC: 70858 AN: 151932 Hom.: 16862 Cov.: 31 AF XY: 0.472 AC XY: 35015 AN XY: 74246

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.481

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: 0.457

Alfa AF: 0.487 Hom.: 2262

Bravo AF: 0.451

Asia WGS AF: 0.559 AC: 1944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.0
DANN	Benign	0.66

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: rs7741515; hg19: chr6-135374368; COSMIC: COSV59020038; COSMIC: COSV59020038;