3-53822023-C-T

Variant names:

• chr3-53822023-C-T
• rs6445606
• NM_018397.5:c.856-247G>A

Variant summary

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

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHDH	NM_018397.5	c.856-247G>A		intron_variant	Intron 4 of 8	ENST00000315251.11	NP_060867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHDH	ENST00000315251.11	c.856-247G>A		intron_variant	Intron 4 of 8	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

African (AFR) AF: 0.870 AC: 36083 AN: 41462

American (AMR) AF: 0.796 AC: 12162 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2361 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5167 AN: 5180

South Asian (SAS) AF: 0.823 AC: 3963 AN: 4816

European-Finnish (FIN) AF: 0.673 AC: 7101 AN: 10556

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46508 AN: 67946

Other (OTH) AF: 0.769 AC: 1622 AN: 2108

Alfa AF: 0.706 Hom.: 89288

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
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6445606; hg19: chr3-53856050;