chr22-28749423-T-C

Position:

• chr22-28749423-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172002.5(HSCB):​c.569-1818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,050 control chromosomes in the GnomAD database, including 4,557 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 0.24 (4557 hom., cov: 31)
• Consequence: HSCB NM_172002.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSCB	NM_172002.5	c.569-1818T>C		intron_variant		ENST00000216027.8	NP_741999.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSCB	ENST00000216027.8	c.569-1818T>C		intron_variant		1	NM_172002.5	ENSP00000216027.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35841 AN: 151930 Hom.: 4550 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.236 AC: 35882 AN: 152050 Hom.: 4557 Cov.: 31 AF XY: 0.241 AC XY: 17883 AN XY: 74324

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.265

Alfa AF: 0.210 Hom.: 2050

Bravo AF: 0.249

Asia WGS AF: 0.368 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs714191; hg19: chr22-29145411;