rs1590975

Positions:

• chr6-135030950-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.430+8623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,818 control chromosomes in the GnomAD database, including 21,186 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 0.53 (21186 hom., cov: 32)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBS1L	NM_006620.4	c.430+8623G>A		intron_variant		ENST00000367837.10	NP_006611.1
HBS1L	NM_001145158.2	c.304+8623G>A		intron_variant			NP_001138630.1
HBS1L	NM_001363686.2	c.-209+8623G>A		intron_variant			NP_001350615.1
HBS1L	XM_047418093.1	c.430+8623G>A		intron_variant			XP_047274049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10	c.430+8623G>A		intron_variant		1	NM_006620.4	ENSP00000356811	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79627 AN: 151700 Hom.: 21150 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.525 AC: 79714 AN: 151818 Hom.: 21186 Cov.: 32 AF XY: 0.529 AC XY: 39210 AN XY: 74132

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.501

Alfa AF: 0.474 Hom.: 3107

Bravo AF: 0.518

Asia WGS AF: 0.575 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.53

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: rs1590975; hg19: chr6-135352088; COSMIC: COSV59019772; COSMIC: COSV59019772;