6-134986347-T-G

Variant names:

• chr6-134986347-T-G
• rs4376364
• NM_006620.4:c.1306-164A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006620.4(HBS1L):​c.1306-164A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,100 control chromosomes in the GnomAD database, including 1,572 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 0.13 (1572 hom., cov: 32)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006620.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	NM_006620.4	MANE Select	c.1306-164A>C		intron	N/A	NP_006611.1
	HBS1L	NM_001145158.2		c.1180-164A>C		intron	N/A	NP_001138630.1
	HBS1L	NM_001363686.2		c.814-164A>C		intron	N/A	NP_001350615.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000367837.10	TSL:1 MANE Select	c.1306-164A>C		intron	N/A	ENSP00000356811.5
	HBS1L	ENST00000527578.5	TSL:1	c.814-164A>C		intron	N/A	ENSP00000436256.1
	HBS1L	ENST00000367826.6	TSL:2	c.1180-164A>C		intron	N/A	ENSP00000356800.2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19826 AN: 151982 Hom.: 1572 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.130 AC: 19829 AN: 152100 Hom.: 1572 Cov.: 32 AF XY: 0.139 AC XY: 10320 AN XY: 74348

African (AFR) AF: 0.0762 AC: 3165 AN: 41518

American (AMR) AF: 0.218 AC: 3324 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1420 AN: 5180

South Asian (SAS) AF: 0.272 AC: 1309 AN: 4818

European-Finnish (FIN) AF: 0.152 AC: 1603 AN: 10578

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8107 AN: 67950

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Alfa AF: 0.107 Hom.: 312

Bravo AF: 0.129

Asia WGS AF: 0.238 AC: 825 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-0.32
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: rs4376364; hg19: chr6-135307485;