1-46315790-G-C

Position:

• chr1-46315790-G-C

Variant summary

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

The NM_006004.4(UQCRH):​c.244-762G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,964 control chromosomes in the GnomAD database, including 34,335 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 0.66 (34335 hom., cov: 31)
• Consequence: UQCRH NM_006004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

UQCRH (HGNC:12590): (ubiquinol-cytochrome c reductase hinge protein) Predicted to enable ubiquinol-cytochrome-c reductase activity. Predicted to be involved in mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

UQCRH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRH	NM_006004.4	c.244-762G>C		intron_variant		ENST00000311672.10	NP_005995.2
UQCRH	NM_001297565.2	c.226-762G>C		intron_variant			NP_001284494.1
UQCRH	NM_001297566.2	c.217-762G>C		intron_variant			NP_001284495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRH	ENST00000311672.10	c.244-762G>C		intron_variant		1	NM_006004.4	ENSP00000309565.5
UQCRH	ENST00000496387.5	n.*83-762G>C		intron_variant		1		ENSP00000477826.1
UQCRH	ENST00000460947.1	n.397-762G>C		intron_variant		2
UQCRH	ENST00000489056.5	n.*83-762G>C		intron_variant		2		ENSP00000484857.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100615 AN: 151846 Hom.: 34328 Cov.: 31

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.662 AC: 100670 AN: 151964 Hom.: 34335 Cov.: 31 AF XY: 0.662 AC XY: 49127 AN XY: 74252

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.694

Alfa AF: 0.595 Hom.: 1931

Bravo AF: 0.656

Asia WGS AF: 0.738 AC: 2563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.64

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: rs4660920; hg19: chr1-46781462;