3-53818026-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018397.5(CHDH):c.1536C>G(p.Pro512=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,614,238 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (5 hom.)
• Consequence: CHDH NM_018397.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 3-53818026-G-C is Benign according to our data. Variant chr3-53818026-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 777801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.035 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHDH	NM_018397.5	c.1536C>G	p.Pro512=	synonymous_variant	9/9	ENST00000315251.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHDH	ENST00000315251.11	c.1536C>G	p.Pro512=	synonymous_variant	9/9	1	NM_018397.5	P1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 237 AN: 152268 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00260

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00143 AC: 359 AN: 251438 Hom.: 2 AF XY: 0.00132 AC XY: 180 AN XY: 135898

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00225

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00222

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00180 AC: 2630 AN: 1461852 Hom.: 5 Cov.: 31 AF XY: 0.00181 AC XY: 1316 AN XY: 727226

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.00216

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152386 Hom.: 0 Cov.: 33 AF XY: 0.00144 AC XY: 107 AN XY: 74516

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000645 Hom.: 0

Bravo AF: 0.00157

EpiCase AF: 0.00311

EpiControl AF: 0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	5.7
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34336629; hg19: chr3-53852053;