6-135028432-C-T

Variant names:

• chr6-135028432-C-T
• rs12661423
• NM_006620.4:c.430+11141G>A

Variant summary

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

The NM_006620.4(HBS1L):​c.430+11141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,808 control chromosomes in the GnomAD database, including 16,233 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 0.45 (16233 hom., cov: 31)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.546 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.430+11141G>A		intron	N/A	NP_006611.1	Q9Y450-1
	HBS1L	NM_001145158.2		c.304+11141G>A		intron	N/A	NP_001138630.1	Q9Y450-4
	HBS1L	NM_001363686.2		c.-209+11141G>A		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.430+11141G>A		intron	N/A	ENSP00000356811.5	Q9Y450-1
	HBS1L	ENST00000949311.1		c.430+11141G>A		intron	N/A	ENSP00000619370.1
	HBS1L	ENST00000881131.1		c.430+11141G>A		intron	N/A	ENSP00000551190.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68979 AN: 151690 Hom.: 16218 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.455 AC: 69019 AN: 151808 Hom.: 16233 Cov.: 31 AF XY: 0.461 AC XY: 34152 AN XY: 74154

African (AFR) AF: 0.329 AC: 13602 AN: 41388

American (AMR) AF: 0.478 AC: 7282 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3466

East Asian (EAS) AF: 0.532 AC: 2750 AN: 5172

South Asian (SAS) AF: 0.563 AC: 2703 AN: 4798

European-Finnish (FIN) AF: 0.586 AC: 6160 AN: 10510

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33517 AN: 67914

Other (OTH) AF: 0.443 AC: 935 AN: 2112

Alfa AF: 0.472 Hom.: 7270

Bravo AF: 0.438

Asia WGS AF: 0.550 AC: 1905 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.58
PhyloP100		-0.14
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: rs12661423; hg19: chr6-135349570; COSMIC: COSV59019686; COSMIC: COSV59019686;