rs113516481

Variant names:

• chr6-134966324-A-C
• rs113516481
• NM_006620.4:c.2043+5T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-134966324-A-C
• chr6-134966324-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006620.4(HBS1L):​c.2043+5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,604,808 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (16 hom.)
• Consequence: HBS1L NM_006620.4 splice_region, intron
• Scores: Splicing: ADA: 0.003293
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.302
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-134966324-A-C is Benign according to our data. Variant chr6-134966324-A-C is described in ClinVar as Benign. ClinVar VariationId is 778253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0055 (837/152286) while in subpopulation AFR AF = 0.0169 (704/41568). AF 95% confidence interval is 0.0159. There are 8 homozygotes in GnomAd4. There are 390 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.2043+5T>G		splice_region intron	N/A	NP_006611.1	Q9Y450-1
	HBS1L	NM_001145158.2		c.1917+5T>G		splice_region intron	N/A	NP_001138630.1	Q9Y450-4
	HBS1L	NM_001363686.2		c.1551+5T>G		splice_region 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.2043+5T>G		splice_region intron	N/A	ENSP00000356811.5	Q9Y450-1
	HBS1L	ENST00000527578.5	TSL:1	c.1551+5T>G		splice_region intron	N/A	ENSP00000436256.1	B7Z524
	HBS1L	ENST00000527005.5	TSL:1	n.1562+5T>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 837 AN: 152168 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00219 AC: 533 AN: 243084 AF XY: 0.00183

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000513

Gnomad OTH exome AF: 0.00237

GnomAD4 exome AF: 0.00102 AC: 1482 AN: 1452522 Hom.: 16 Cov.: 30 AF XY: 0.000961 AC XY: 694 AN XY: 722260

African (AFR) AF: 0.0190 AC: 625 AN: 32978

American (AMR) AF: 0.00144 AC: 62 AN: 42996

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 277 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.000167 AC: 14 AN: 83966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53060

Middle Eastern (MID) AF: 0.00489 AC: 28 AN: 5724

European-Non Finnish (NFE) AF: 0.000294 AC: 326 AN: 1108462

Other (OTH) AF: 0.00250 AC: 150 AN: 59992

GnomAD4 genome AF: 0.00550 AC: 837 AN: 152286 Hom.: 8 Cov.: 32 AF XY: 0.00524 AC XY: 390 AN XY: 74468

African (AFR) AF: 0.0169 AC: 704 AN: 41568

American (AMR) AF: 0.00320 AC: 49 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68002

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00337 Hom.: 7

Bravo AF: 0.00644

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.62
PhyloP100		-0.30
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0033
dbscSNV1_RF	Benign	0.070
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: rs113516481; hg19: chr6-135287462;