rs2297339

Variant names:

• chr6-135054853-G-A
• rs2297339
• ENST00000367822.9:c.-162C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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]

ENSG00000232876 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HBS1L	NM_006620.4	c.-162C>T		upstream_gene_variant		ENST00000367837.10	NP_006611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBS1L	ENST00000367837.10	c.-162C>T		upstream_gene_variant		1	NM_006620.4	ENSP00000356811.5

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

African (AFR) AF: 0.365 AC: 5899 AN: 16140

American (AMR) AF: 0.501 AC: 13591 AN: 27120

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 7229 AN: 16296

East Asian (EAS) AF: 0.552 AC: 17623 AN: 31936

South Asian (SAS) AF: 0.561 AC: 30749 AN: 54764

European-Finnish (FIN) AF: 0.485 AC: 15834 AN: 32618

Middle Eastern (MID) AF: 0.398 AC: 1014 AN: 2548

European-Non Finnish (NFE) AF: 0.430 AC: 166988 AN: 388700

Other (OTH) AF: 0.451 AC: 14104 AN: 31256

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

African (AFR) AF: 0.359 AC: 14895 AN: 41512

American (AMR) AF: 0.462 AC: 7074 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2735 AN: 5154

South Asian (SAS) AF: 0.557 AC: 2692 AN: 4834

European-Finnish (FIN) AF: 0.491 AC: 5199 AN: 10598

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29610 AN: 67966

Other (OTH) AF: 0.432 AC: 912 AN: 2110

Alfa AF: 0.436 Hom.: 5981

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
PhyloP100		2.4
PromoterAI		0.0074	Neutral
Mutation Taster		=299/1	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: rs2297339; hg19: chr6-135375991; COSMIC: COSV59020707; COSMIC: COSV59020707;