rs4563403

Variant names:

• chr3-53816787-C-T
• rs4563403
• NM_018397.5:c.*990G>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.*990G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 150,556 control chromosomes in the GnomAD database, including 4,828 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 0.22 (4828 hom., cov: 30)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: CHDH NM_018397.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 14 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHDH	NM_018397.5	c.*990G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000315251.11	NP_060867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHDH	ENST00000315251.11	c.*990G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_018397.5	ENSP00000319851.5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32447 AN: 150444 Hom.: 4813 Cov.: 30

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 1 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.216 AC: 32506 AN: 150540 Hom.: 4828 Cov.: 30 AF XY: 0.216 AC XY: 15854 AN XY: 73424

African (AFR) AF: 0.417 AC: 16981 AN: 40706

American (AMR) AF: 0.238 AC: 3605 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3468

East Asian (EAS) AF: 0.168 AC: 860 AN: 5116

South Asian (SAS) AF: 0.118 AC: 561 AN: 4766

European-Finnish (FIN) AF: 0.134 AC: 1370 AN: 10194

Middle Eastern (MID) AF: 0.156 AC: 45 AN: 288

European-Non Finnish (NFE) AF: 0.119 AC: 8093 AN: 67866

Other (OTH) AF: 0.198 AC: 413 AN: 2088

Alfa AF: 0.153 Hom.: 1675

Bravo AF: 0.236

Asia WGS AF: 0.169 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.0
DANN	Benign	0.57
PhyloP100		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4563403; hg19: chr3-53850814;