NM_017812.4:c.454-17041G>A

Variant names:

• chr7-132855510-C-T
• rs10488661
• NM_017812.4:c.454-17041G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017812.4(CHCHD3):​c.454-17041G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,006 control chromosomes in the GnomAD database, including 4,236 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 0.23 (4236 hom., cov: 32)
• Consequence: CHCHD3 NM_017812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 3 publications found

Genes affected

CHCHD3 (HGNC:21906): (coiled-coil-helix-coiled-coil-helix domain containing 3) The protein encoded by this gene is an inner mitochondrial membrane scaffold protein. Absence of the encoded protein affects the structural integrity of mitochondrial cristae and leads to reductions in ATP production, cell growth, and oxygen consumption. This protein is part of the mitochondrial contact site and cristae organizing system (MICOS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD3	NM_017812.4	c.454-17041G>A		intron_variant	Intron 5 of 7	ENST00000262570.10	NP_060282.1
CHCHD3	NM_001317177.2	c.469-17041G>A		intron_variant	Intron 6 of 8		NP_001304106.1
CHCHD3	NR_133671.2	n.697-17041G>A		intron_variant	Intron 6 of 10
CHCHD3	XM_047420549.1	c.358-17041G>A		intron_variant	Intron 5 of 7		XP_047276505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCHD3	ENST00000262570.10	c.454-17041G>A		intron_variant	Intron 5 of 7	1	NM_017812.4	ENSP00000262570.5
CHCHD3	ENST00000423635.5	n.544-17041G>A		intron_variant	Intron 6 of 10	1		ENSP00000410425.1
CHCHD3	ENST00000448878.6	c.469-17041G>A		intron_variant	Intron 6 of 8	5		ENSP00000389297.2
CHCHD3	ENST00000496427.5	n.364-17041G>A		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35054 AN: 151888 Hom.: 4230 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.231 AC: 35088 AN: 152006 Hom.: 4236 Cov.: 32 AF XY: 0.232 AC XY: 17242 AN XY: 74280

African (AFR) AF: 0.208 AC: 8608 AN: 41452

American (AMR) AF: 0.225 AC: 3437 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3472

East Asian (EAS) AF: 0.0940 AC: 486 AN: 5168

South Asian (SAS) AF: 0.260 AC: 1252 AN: 4812

European-Finnish (FIN) AF: 0.317 AC: 3343 AN: 10544

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16488 AN: 67952

Other (OTH) AF: 0.225 AC: 476 AN: 2114

Alfa AF: 0.227 Hom.: 494

Bravo AF: 0.225

Asia WGS AF: 0.175 AC: 610 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.42
PhyloP100		1.9
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: rs10488661; hg19: chr7-132540270;