Variant 1-18871606-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003748.4(ALDH4A1):c.*1239G>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 0.235 in 152,310 control chromosomes in the GnomAD database, including 4,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4487 hom., cov: 33)

Exomes 𝑓: 0.25 ( 5 hom. )

Consequence

ALDH4A1
NM_003748.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.122

Variant links:

Genes affected

ALDH4A1 (HGNC:406): (aldehyde dehydrogenase 4 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]

ALDH4A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-18871606-C-G is Benign according to our data. Variant chr1-18871606-C-G is described in ClinVar as [Benign]. Clinvar id is 294334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ALDH4A1	NM_003748.4 linkuse as main transcript	c.*1239G>C	3_prime_UTR_variant	15/15	ENST00000375341.8
ALDH4A1	NM_001161504.2 linkuse as main transcript	c.*1239G>C	3_prime_UTR_variant	15/15
ALDH4A1	NM_001319218.2 linkuse as main transcript	c.*1239G>C	3_prime_UTR_variant	14/14
ALDH4A1	NM_170726.3 linkuse as main transcript	c.*226G>C	3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH4A1	ENST00000375341.8 linkuse as main transcript	c.*1239G>C	3_prime_UTR_variant	15/15	1	NM_003748.4	P1	P30038-1
ALDH4A1	ENST00000290597.9 linkuse as main transcript	c.*226G>C	3_prime_UTR_variant	16/16	1		P1	P30038-1
ALDH4A1	ENST00000538839.5 linkuse as main transcript	c.*1239G>C	3_prime_UTR_variant	14/14	1			P30038-3

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35720

AN:

152060

Hom.:

4485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.245

GnomAD4 exome

AF:

0.250

AC:

AN:

132

Hom.:

Cov.:

AF XY:

0.213

AC XY:

AN XY:

108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.235

AC:

35729

AN:

152178

Hom.:

4487

Cov.:

AF XY:

0.228

AC XY:

16963

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.243

Hom.:

589

Bravo

AF:

0.237

Asia WGS

AF:

0.0730

AC:

259

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hyperprolinemia type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.8

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over