chr6-135014038-G-C

Variant names:

• chr6-135014038-G-C
• rs6923765
• NM_006620.4:c.431-11196C>G

Variant summary

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

The NM_006620.4(HBS1L):​c.431-11196C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,906 control chromosomes in the GnomAD database, including 16,687 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 0.46 (16687 hom., cov: 31)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.545 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	NM_006620.4	MANE Select	c.431-11196C>G		intron	N/A	NP_006611.1	Q9Y450-1
	HBS1L	NM_001145158.2		c.305-11196C>G		intron	N/A	NP_001138630.1	Q9Y450-4
	HBS1L	NM_001363686.2		c.-208-3279C>G		intron	N/A	NP_001350615.1	B7Z524

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000367837.10	TSL:1 MANE Select	c.431-11196C>G		intron	N/A	ENSP00000356811.5	Q9Y450-1
	HBS1L	ENST00000527578.5	TSL:1	c.-62-11196C>G		intron	N/A	ENSP00000436256.1	B7Z524
	HBS1L	ENST00000949311.1		c.431-11196C>G		intron	N/A	ENSP00000619370.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70281 AN: 151788 Hom.: 16668 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.463 AC: 70328 AN: 151906 Hom.: 16687 Cov.: 31 AF XY: 0.468 AC XY: 34760 AN XY: 74246

African (AFR) AF: 0.355 AC: 14707 AN: 41428

American (AMR) AF: 0.482 AC: 7361 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1676 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2743 AN: 5166

South Asian (SAS) AF: 0.563 AC: 2704 AN: 4802

European-Finnish (FIN) AF: 0.585 AC: 6162 AN: 10532

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33580 AN: 67926

Other (OTH) AF: 0.452 AC: 955 AN: 2112

Alfa AF: 0.352 Hom.: 975

Bravo AF: 0.448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.30
PhyloP100		1.1
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: rs6923765; hg19: chr6-135335176; COSMIC: COSV59019551;