rs4896128

Variant names:

• chr6-135028618-G-A
• rs4896128
• NM_006620.4:c.430+10955C>T

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+10955C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,902 control chromosomes in the GnomAD database, including 7,884 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 0.31 (7884 hom., cov: 32)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBS1L	NM_006620.4	c.430+10955C>T		intron_variant	Intron 4 of 17	ENST00000367837.10	NP_006611.1
HBS1L	NM_001145158.2	c.304+10955C>T		intron_variant	Intron 3 of 16		NP_001138630.1
HBS1L	NM_001363686.2	c.-209+10955C>T		intron_variant	Intron 4 of 18		NP_001350615.1
HBS1L	XM_047418093.1	c.430+10955C>T		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+10955C>T		intron_variant	Intron 4 of 17	1	NM_006620.4	ENSP00000356811.5

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47641 AN: 151784 Hom.: 7876 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.314 AC: 47671 AN: 151902 Hom.: 7884 Cov.: 32 AF XY: 0.311 AC XY: 23122 AN XY: 74232

African (AFR) AF: 0.217 AC: 9007 AN: 41482

American (AMR) AF: 0.256 AC: 3903 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1126 AN: 3462

East Asian (EAS) AF: 0.257 AC: 1330 AN: 5172

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4810

European-Finnish (FIN) AF: 0.434 AC: 4562 AN: 10510

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25380 AN: 67888

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.345 Hom.: 25198

Bravo AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.63
PhyloP100		-0.72
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: rs4896128; hg19: chr6-135349756; COSMIC: COSV59019694; COSMIC: COSV59019694;