rs6474051

Variant names:

• chr8-56212711-T-C
• rs6474051
• NM_001011671.3:c.-17+874T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHCHD7	NM_001011671.3	c.-17+874T>C		intron_variant	Intron 1 of 3	ENST00000355315.8	NP_001011671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCHD7	ENST00000355315.8	c.-17+874T>C		intron_variant	Intron 1 of 3	2	NM_001011671.3	ENSP00000347469.3

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

African (AFR) AF: 0.830 AC: 10586 AN: 12748

American (AMR) AF: 0.792 AC: 15952 AN: 20146

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 11114 AN: 14058

East Asian (EAS) AF: 0.944 AC: 29586 AN: 31342

South Asian (SAS) AF: 0.703 AC: 29813 AN: 42404

European-Finnish (FIN) AF: 0.767 AC: 34121 AN: 44466

Middle Eastern (MID) AF: 0.813 AC: 2358 AN: 2900

European-Non Finnish (NFE) AF: 0.767 AC: 209992 AN: 273640

Other (OTH) AF: 0.786 AC: 20798 AN: 26464

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

African (AFR) AF: 0.829 AC: 34370 AN: 41484

American (AMR) AF: 0.777 AC: 11879 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2744 AN: 3470

East Asian (EAS) AF: 0.944 AC: 4882 AN: 5172

South Asian (SAS) AF: 0.715 AC: 3450 AN: 4828

European-Finnish (FIN) AF: 0.773 AC: 8167 AN: 10564

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51946 AN: 68004

Other (OTH) AF: 0.805 AC: 1696 AN: 2106

Alfa AF: 0.781 Hom.: 67477

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
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6474051; hg19: chr8-57125270;