1-46315930-G-T

Position:

• chr1-46315930-G-T

Variant summary

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

The NM_006004.4(UQCRH):​c.244-622G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,956 control chromosomes in the GnomAD database, including 34,343 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 (34343 hom., cov: 32)
• Consequence: UQCRH NM_006004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCRH	NM_006004.4	c.244-622G>T		intron_variant		ENST00000311672.10
UQCRH	NM_001297565.2	c.226-622G>T		intron_variant
UQCRH	NM_001297566.2	c.217-622G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCRH	ENST00000311672.10	c.244-622G>T		intron_variant		1	NM_006004.4	P1
UQCRH	ENST00000496387.5	c.*83-622G>T		intron_variant, NMD_transcript_variant		1
UQCRH	ENST00000489056.5	c.*83-622G>T		intron_variant, NMD_transcript_variant		2
UQCRH	ENST00000460947.1	n.397-622G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100621 AN: 151838 Hom.: 34336 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.759

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: 0.663 AC: 100676 AN: 151956 Hom.: 34343 Cov.: 32 AF XY: 0.662 AC XY: 49139 AN XY: 74274

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.694

Alfa AF: 0.734 Hom.: 41800

Bravo AF: 0.656

Asia WGS AF: 0.736 AC: 2555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.5
DANN	Benign	0.71

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: rs4660921; hg19: chr1-46781602;