rs2297339

Positions:

• chr6-135054853-G-A
• chr6-135054853-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000367822.9(HBS1L):​c.-162C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 753,524 control chromosomes in the GnomAD database, including 76,999 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 0.43 (14091 hom., cov: 33)
  • Exomes 𝑓: 0.45 (62908 hom.)
• Consequence: HBS1L ENST00000367822.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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]

LOC124901405 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBS1L	NM_006620.4			upstream_gene_variant		ENST00000367837.10	NP_006611.1
LOC124901405	XR_007059775.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10			upstream_gene_variant		1	NM_006620.4	ENSP00000356811	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65010 AN: 152028 Hom.: 14070 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.454 AC: 273031 AN: 601378 Hom.: 62908 Cov.: 8 AF XY: 0.459 AC XY: 144013 AN XY: 313414

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.552

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.428 AC: 65063 AN: 152146 Hom.: 14091 Cov.: 33 AF XY: 0.433 AC XY: 32209 AN XY: 74380

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.432

Alfa AF: 0.440 Hom.: 4912

Bravo AF: 0.420

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.92

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: rs2297339; hg19: chr6-135375991; COSMIC: COSV59020707; COSMIC: COSV59020707;