rs1014021

Variant names:

• chr6-135013462-A-G
• rs1014021
• NM_006620.4:c.431-10620T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-135013462-A-G
• chr6-135013462-A-T

Variant summary

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

The NM_006620.4(HBS1L):​c.431-10620T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,026 control chromosomes in the GnomAD database, including 21,467 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 0.53 (21467 hom., cov: 32)
• Consequence: HBS1L NM_006620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 16 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 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.431-10620T>C		intron	N/A	NP_006611.1
	HBS1L	NM_001145158.2		c.305-10620T>C		intron	N/A	NP_001138630.1
	HBS1L	NM_001363686.2		c.-208-2703T>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.431-10620T>C		intron	N/A	ENSP00000356811.5
	HBS1L	ENST00000527578.5	TSL:1	c.-62-10620T>C		intron	N/A	ENSP00000436256.1
	HBS1L	ENST00000367826.6	TSL:2	c.305-10620T>C		intron	N/A	ENSP00000356800.2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80391 AN: 151908 Hom.: 21426 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.529 AC: 80486 AN: 152026 Hom.: 21467 Cov.: 32 AF XY: 0.532 AC XY: 39532 AN XY: 74298

African (AFR) AF: 0.583 AC: 24160 AN: 41440

American (AMR) AF: 0.509 AC: 7783 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3466

East Asian (EAS) AF: 0.530 AC: 2745 AN: 5176

South Asian (SAS) AF: 0.565 AC: 2723 AN: 4822

European-Finnish (FIN) AF: 0.586 AC: 6188 AN: 10566

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.496 AC: 33685 AN: 67962

Other (OTH) AF: 0.509 AC: 1076 AN: 2114

Alfa AF: 0.504 Hom.: 83045

Bravo AF: 0.525

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.7
DANN	Benign	0.35
PhyloP100		-2.7
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: rs1014021; hg19: chr6-135334600; COSMIC: COSV59019547;