rs6474051

Positions:

• chr8-56212711-T-C

Variant summary

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

The NM_001011671.3(CHCHD7):​c.-17+874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 620,290 control chromosomes in the GnomAD database, including 190,262 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 0.79 (47673 hom., cov: 32)
  • Exomes 𝑓: 0.78 (142589 hom.)
• Consequence: CHCHD7 NM_001011671.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660

Genes affected

CHCHD7 (HGNC:28314): (coiled-coil-helix-coiled-coil-helix domain containing 7) Predicted to be located in mitochondrial intermembrane space. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHCHD7	NM_001011671.3	c.-17+874T>C		intron_variant		ENST00000355315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHCHD7	ENST00000355315.8	c.-17+874T>C		intron_variant		2	NM_001011671.3	P1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120103 AN: 152004 Hom.: 47615 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.778 AC: 364320 AN: 468168 Hom.: 142589 Cov.: 5 AF XY: 0.774 AC XY: 192614 AN XY: 248744

Gnomad4 AFR exome AF: 0.830

Gnomad4 AMR exome AF: 0.792

Gnomad4 ASJ exome AF: 0.791

Gnomad4 EAS exome AF: 0.944

Gnomad4 SAS exome AF: 0.703

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.786

GnomAD4 genome AF: 0.790 AC: 120221 AN: 152122 Hom.: 47673 Cov.: 32 AF XY: 0.788 AC XY: 58613 AN XY: 74346

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.805

Alfa AF: 0.783 Hom.: 12254

Bravo AF: 0.797

Asia WGS AF: 0.826 AC: 2874 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	4.4
DANN	Benign	0.51

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: rs6474051; hg19: chr8-57125270;