rs28384513

Variant names:

• chr6-135055071-T-G
• rs28384513
• ENST00000529882.5:c.89-4424A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-135055071-T-G
• chr6-135055071-T-A
• chr6-135055071-T-C

Variant summary

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

The ENST00000529882.5(HBS1L):​c.89-4424A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 418,216 control chromosomes in the GnomAD database, including 24,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.31 (7870 hom., cov: 33)
  • Exomes 𝑓: 0.35 (16941 hom.)
• Consequence: HBS1L ENST00000529882.5 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.27
• Publications: 47 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]

ENSG00000232876 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529882.5. 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.-380A>C		upstream_gene	N/A	NP_006611.1	Q9Y450-1
	HBS1L	NM_001145158.2		c.-380A>C		upstream_gene	N/A	NP_001138630.1	Q9Y450-4
	HBS1L	NM_001145207.2		c.-380A>C		upstream_gene	N/A	NP_001138679.1	Q9Y450-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBS1L	ENST00000529882.5	TSL:4	c.89-4424A>C		intron	N/A	ENSP00000433030.1	E9PMN1
	ENSG00000232876	ENST00000447508.2	TSL:2	n.80T>G		non_coding_transcript_exon	Exon 1 of 2
	HBS1L	ENST00000367837.10	TSL:1 MANE Select	c.-380A>C		upstream_gene	N/A	ENSP00000356811.5	Q9Y450-1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47587 AN: 152102 Hom.: 7863 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.355 AC: 94332 AN: 265996 Hom.: 16941 Cov.: 0 AF XY: 0.354 AC XY: 48037 AN XY: 135536

African (AFR) AF: 0.219 AC: 1687 AN: 7706

American (AMR) AF: 0.257 AC: 2360 AN: 9174

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 3022 AN: 9528

East Asian (EAS) AF: 0.305 AC: 7148 AN: 23400

South Asian (SAS) AF: 0.301 AC: 2358 AN: 7822

European-Finnish (FIN) AF: 0.419 AC: 8878 AN: 21212

Middle Eastern (MID) AF: 0.259 AC: 350 AN: 1352

European-Non Finnish (NFE) AF: 0.373 AC: 62879 AN: 168592

Other (OTH) AF: 0.328 AC: 5650 AN: 17210

GnomAD4 genome AF: 0.313 AC: 47615 AN: 152220 Hom.: 7870 Cov.: 33 AF XY: 0.310 AC XY: 23106 AN XY: 74434

African (AFR) AF: 0.214 AC: 8892 AN: 41540

American (AMR) AF: 0.255 AC: 3907 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1126 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1331 AN: 5182

South Asian (SAS) AF: 0.291 AC: 1404 AN: 4828

European-Finnish (FIN) AF: 0.432 AC: 4578 AN: 10592

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25417 AN: 67992

Other (OTH) AF: 0.285 AC: 604 AN: 2116

Alfa AF: 0.276 Hom.: 1527

Bravo AF: 0.297

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.71
PhyloP100		-1.3
PromoterAI		-0.014	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28384513; hg19: chr6-135376209; COSMIC: COSV59019354;