6-135031510-G-C

Variant names:

• chr6-135031510-G-C
• rs9321481
• NM_006620.4:c.430+8063C>G

Variant summary

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

The NM_006620.4(HBS1L):​c.430+8063C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,790 control chromosomes in the GnomAD database, including 18,447 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 0.49 (18447 hom., cov: 32)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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 = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBS1L	NM_006620.4	c.430+8063C>G		intron_variant	Intron 4 of 17	ENST00000367837.10	NP_006611.1
HBS1L	NM_001145158.2	c.304+8063C>G		intron_variant	Intron 3 of 16		NP_001138630.1
HBS1L	NM_001363686.2	c.-209+8063C>G		intron_variant	Intron 4 of 18		NP_001350615.1
HBS1L	XM_047418093.1	c.430+8063C>G		intron_variant	Intron 4 of 15		XP_047274049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10	c.430+8063C>G		intron_variant	Intron 4 of 17	1	NM_006620.4	ENSP00000356811.5

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74208 AN: 151674 Hom.: 18422 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.489 AC: 74275 AN: 151790 Hom.: 18447 Cov.: 32 AF XY: 0.495 AC XY: 36671 AN XY: 74104

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.474

Alfa AF: 0.494 Hom.: 2268

Bravo AF: 0.476

Asia WGS AF: 0.568 AC: 1975 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	4.4
DANN	Benign	0.57

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: rs9321481; hg19: chr6-135352648;