chr3-53822023-C-T

Position:

• chr3-53822023-C-T

Variant summary

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

The NM_018397.5(CHDH):​c.856-247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,026 control chromosomes in the GnomAD database, including 44,763 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 0.76 (44763 hom., cov: 30)
• Consequence: CHDH NM_018397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.86).
• 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.856-247G>A		intron_variant		ENST00000315251.11	NP_060867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHDH	ENST00000315251.11	c.856-247G>A		intron_variant		1	NM_018397.5	ENSP00000319851.5

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115635 AN: 151908 Hom.: 44705 Cov.: 30

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.761 AC: 115752 AN: 152026 Hom.: 44763 Cov.: 30 AF XY: 0.765 AC XY: 56841 AN XY: 74314

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.769

Alfa AF: 0.698 Hom.: 55562

Bravo AF: 0.775

Asia WGS AF: 0.917 AC: 3188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.32
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6445606; hg19: chr3-53856050;