chr22-28757771-C-T

Variant names:

• chr22-28757771-C-T
• rs5752792
• ENST00000913000.1:c.*602C>T

Variant summary

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

The ENST00000913000.1(HSCB):​c.*602C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,120 control chromosomes in the GnomAD database, including 58,834 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 0.88 (58834 hom., cov: 30)
• Consequence: HSCB ENST00000913000.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 14 publications found

Genes affected

HSCB (HGNC:28913): (HscB mitochondrial iron-sulfur cluster cochaperone) This gene encodes a DnaJ-type co-chaperone and member of the heat shock cognate B (HscB) family of proteins. The encoded protein plays a role in the synthesis of iron-sulfur clusters, protein cofactors that are involved in the redox reactions of mitochondrial electron transport and other processes. Cells in which this gene is knocked down exhibit reduced activity of iron-sulfur cluster-dependent enzymes including succinate dehydrogenase and aconitase. The encoded protein may stimulate the ATPase activity of the mitochondrial stress-70 protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

HSCB Gene-Disease associations (from GenCC):

• anemia, sideroblastic, 5

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000913000.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSCB	ENST00000913000.1		c.*602C>T		downstream_gene	N/A	ENSP00000583059.1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133162 AN: 152000 Hom.: 58763 Cov.: 30

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.876 AC: 133294 AN: 152120 Hom.: 58834 Cov.: 30 AF XY: 0.881 AC XY: 65546 AN XY: 74384

African (AFR) AF: 0.968 AC: 40159 AN: 41508

American (AMR) AF: 0.874 AC: 13314 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2946 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5162 AN: 5170

South Asian (SAS) AF: 0.957 AC: 4621 AN: 4828

European-Finnish (FIN) AF: 0.866 AC: 9178 AN: 10594

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55213 AN: 67990

Other (OTH) AF: 0.867 AC: 1832 AN: 2114

Alfa AF: 0.833 Hom.: 44558

Bravo AF: 0.878

Asia WGS AF: 0.972 AC: 3378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		0.062

Splicing

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

Other links and lift over

dbSNP: rs5752792; hg19: chr22-29153759;