chr22-28749551-C-T

Position:

• chr22-28749551-C-T

Variant summary

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

The NM_172002.5(HSCB):​c.569-1690C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,218 control chromosomes in the GnomAD database, including 454 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 0.070 (454 hom., cov: 31)
• Consequence: HSCB NM_172002.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSCB	NM_172002.5	c.569-1690C>T		intron_variant		ENST00000216027.8	NP_741999.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSCB	ENST00000216027.8	c.569-1690C>T		intron_variant		1	NM_172002.5	ENSP00000216027.3

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10671 AN: 152100 Hom.: 448 Cov.: 31

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0702 AC: 10692 AN: 152218 Hom.: 454 Cov.: 31 AF XY: 0.0731 AC XY: 5443 AN XY: 74418

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.0583

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.0512

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0623 Hom.: 122

Bravo AF: 0.0653

Asia WGS AF: 0.142 AC: 493 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.79

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: rs5997391; hg19: chr22-29145539;