rs1590975

Variant names:

• chr6-135030950-C-T
• rs1590975
• NM_006620.4:c.430+8623G>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.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
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006620.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	NM_006620.4	MANE Select	c.430+8623G>A		intron	N/A	NP_006611.1
	HBS1L	NM_001145158.2		c.304+8623G>A		intron	N/A	NP_001138630.1
	HBS1L	NM_001363686.2		c.-209+8623G>A		intron	N/A	NP_001350615.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000367837.10	TSL:1 MANE Select	c.430+8623G>A		intron	N/A	ENSP00000356811.5
	HBS1L	ENST00000367826.6	TSL:2	c.304+8623G>A		intron	N/A	ENSP00000356800.2
	HBS1L	ENST00000415177.6	TSL:5	c.235+11051G>A		intron	N/A	ENSP00000389826.2

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

African (AFR) AF: 0.564 AC: 23375 AN: 41456

American (AMR) AF: 0.502 AC: 7663 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1675 AN: 3468

East Asian (EAS) AF: 0.533 AC: 2752 AN: 5168

South Asian (SAS) AF: 0.566 AC: 2723 AN: 4814

European-Finnish (FIN) AF: 0.611 AC: 6343 AN: 10386

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33679 AN: 67940

Other (OTH) AF: 0.501 AC: 1057 AN: 2110

Alfa AF: 0.493 Hom.: 7098

Bravo AF: 0.518

Asia WGS AF: 0.575 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.53
PhyloP100		-0.86
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: rs1590975; hg19: chr6-135352088; COSMIC: COSV59019772; COSMIC: COSV59019772;