chr6-135054853-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000367822.9(HBS1L):​c.-162C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 602,376 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: HBS1L ENST00000367822.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBS1L	NM_006620.4	c.-162C>G		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>G		upstream_gene_variant		1	NM_006620.4	ENSP00000356811.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000332 AC: 2 AN: 602376 Hom.: 0 Cov.: 8 AF XY: 0.00000319 AC XY: 1 AN XY: 313902

African (AFR) AF: 0.00 AC: 0 AN: 16164

American (AMR) AF: 0.00 AC: 0 AN: 27170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16316

East Asian (EAS) AF: 0.00 AC: 0 AN: 31960

South Asian (SAS) AF: 0.0000182 AC: 1 AN: 54838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2550

European-Non Finnish (NFE) AF: 0.00000257 AC: 1 AN: 389456

Other (OTH) AF: 0.00 AC: 0 AN: 31284

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		2.4
PromoterAI		0.0027	Neutral

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;