NM_006620.4:c.44-1291C>A

Variant names:

• chr6-135051938-G-T
• rs1041480
• NM_006620.4:c.44-1291C>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.44-1291C>A 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 152,036 control chromosomes in the GnomAD database, including 16,870 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 (16870 hom., cov: 32)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 11 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=-0.74).
• 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.44-1291C>A		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.44-1291C>A		intron_variant	Intron 1 of 17	1	NM_006620.4	ENSP00000356811.5

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70861 AN: 151918 Hom.: 16851 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.466 AC: 70912 AN: 152036 Hom.: 16870 Cov.: 32 AF XY: 0.472 AC XY: 35034 AN XY: 74302

African (AFR) AF: 0.368 AC: 15268 AN: 41434

American (AMR) AF: 0.481 AC: 7355 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1636 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2751 AN: 5180

South Asian (SAS) AF: 0.563 AC: 2718 AN: 4824

European-Finnish (FIN) AF: 0.585 AC: 6167 AN: 10544

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33618 AN: 67986

Other (OTH) AF: 0.456 AC: 960 AN: 2106

Alfa AF: 0.448 Hom.: 7206

Bravo AF: 0.451

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.6
DANN	Benign	0.84
PhyloP100		-0.31
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: rs1041480; hg19: chr6-135373076; COSMIC: COSV59020016; COSMIC: COSV59020016;