rs1530691

Positions:

• chr3-126847004-G-A
• chr3-126847004-G-C

Variant summary

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

The NM_032343.3(CHCHD6):​c.412-5643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,166 control chromosomes in the GnomAD database, including 2,492 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 0.16 (2492 hom., cov: 33)
• Consequence: CHCHD6 NM_032343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

Genes affected

CHCHD6 (HGNC:28184): (coiled-coil-helix-coiled-coil-helix domain containing 6) Involved in cellular response to DNA damage stimulus and cristae formation. Located in cytosol and mitochondrial inner membrane. Part of MICOS complex. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHCHD6	NM_032343.3	c.412-5643G>A		intron_variant		ENST00000290913.8	NP_115719.1
CHCHD6	NM_001320610.2	c.412-5640G>A		intron_variant			NP_001307539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHCHD6	ENST00000290913.8	c.412-5643G>A		intron_variant		1	NM_032343.3	ENSP00000290913	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23899 AN: 152048 Hom.: 2491 Cov.: 33

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.157 AC: 23894 AN: 152166 Hom.: 2492 Cov.: 33 AF XY: 0.155 AC XY: 11533 AN XY: 74386

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.00751

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.145

Alfa AF: 0.215 Hom.: 6098

Bravo AF: 0.143

Asia WGS AF: 0.0780 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.69

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: rs1530691; hg19: chr3-126565847;