rs113665733

Variant names:

• chr6-135042106-G-A
• rs113665733
• NM_006620.4:c.130C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001363686.2(HBS1L):​c.-509C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000443 in 1,612,452 control chromosomes in the GnomAD database, including 5 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 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (4 hom.)
• Consequence: HBS1L NM_001363686.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 4 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010869116).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363686.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	NM_006620.4	MANE Select	c.130C>T	p.Arg44Trp	missense	Exon 3 of 18	NP_006611.1
	HBS1L	NM_001363686.2		c.-509C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 19	NP_001350615.1
	HBS1L	NM_001145207.2		c.130C>T	p.Arg44Trp	missense	Exon 3 of 5	NP_001138679.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000367837.10	TSL:1 MANE Select	c.130C>T	p.Arg44Trp	missense	Exon 3 of 18	ENSP00000356811.5
	HBS1L	ENST00000367822.9	TSL:1	c.130C>T	p.Arg44Trp	missense	Exon 3 of 5	ENSP00000356796.5
	HBS1L	ENST00000949311.1		c.130C>T	p.Arg44Trp	missense	Exon 3 of 19	ENSP00000619370.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152136 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000639 AC: 160 AN: 250386 AF XY: 0.000517

Gnomad AFR exome AF: 0.00816

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000240 AC: 351 AN: 1460198 Hom.: 4 Cov.: 30 AF XY: 0.000245 AC XY: 178 AN XY: 726402

African (AFR) AF: 0.00765 AC: 256 AN: 33444

American (AMR) AF: 0.000537 AC: 24 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39608

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.000353 AC: 2 AN: 5658

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111018

Other (OTH) AF: 0.000332 AC: 20 AN: 60302

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152254 Hom.: 1 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74438

African (AFR) AF: 0.00799 AC: 332 AN: 41552

American (AMR) AF: 0.00157 AC: 24 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68000

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.00275

ESP6500AA AF: 0.00545 AC: 24

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000824 AC: 100

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.1
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.2	D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.64
MVP		0.65
MPC		0.63
ClinPred		0.083	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.22
gMVP		0.65
Mutation Taster		=91/9	polymorphism

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: rs113665733; hg19: chr6-135363244;