3-53815483-A-G

Position:

• chr3-53815483-A-G

Variant summary

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

The NM_018397.5(CHDH):​c.*2294T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,244 control chromosomes in the GnomAD database, including 47,043 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 0.78 (47036 hom., cov: 33)
  • Exomes 𝑓: 0.73 (7 hom.)
• Consequence: CHDH NM_018397.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

Genes affected

CHDH (HGNC:24288): (choline dehydrogenase) The protein encoded by this gene is a choline dehydrogenase that localizes to the mitochondrion. Variations in this gene can affect susceptibility to choline deficiency. A few transcript variants have been found for this gene, but the full-length nature of only one has been characterized to date. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHDH	NM_018397.5	c.*2294T>C		3_prime_UTR_variant	9/9	ENST00000315251.11	NP_060867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHDH	ENST00000315251.11	c.*2294T>C		3_prime_UTR_variant	9/9	1	NM_018397.5	ENSP00000319851	P1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118395 AN: 152100 Hom.: 46970 Cov.: 33

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.780

GnomAD4 exome AF: 0.731 AC: 19 AN: 26 Hom.: 7 Cov.: 0 AF XY: 0.682 AC XY: 15 AN XY: 22

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.779 AC: 118521 AN: 152218 Hom.: 47036 Cov.: 33 AF XY: 0.781 AC XY: 58115 AN XY: 74414

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.783

Alfa AF: 0.748 Hom.: 14212

Bravo AF: 0.794

Asia WGS AF: 0.918 AC: 3194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.61

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: rs4687587; hg19: chr3-53849510;