rs79544459

Positions:

chr5-126577223-A-C

Variant summary

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

The NM_001182.5(ALDH7A1):c.518-12T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 1,614,016 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 118 hom., cov: 31)

Exomes 𝑓: 0.020 ( 389 hom. )

Consequence

ALDH7A1
NM_001182.5 intron

Scores

Splicing: ADA: 0.0001611

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.192

Variant links:

Genes affected

ALDH7A1 (HGNC:877): (aldehyde dehydrogenase 7 family member A1) The protein encoded by this gene is a member of subfamily 7 in the aldehyde dehydrogenase gene family. These enzymes are thought to play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. This particular member has homology to a previously described protein from the green garden pea, the 26g pea turgor protein. It is also involved in lysine catabolism that is known to occur in the mitochondrial matrix. Recent reports show that this protein is found both in the cytosol and the mitochondria, and the two forms likely arise from the use of alternative translation initiation sites. An additional variant encoding a different isoform has also been found for this gene. Mutations in this gene are associated with pyridoxine-dependent epilepsy. Several related pseudogenes have also been identified. [provided by RefSeq, Jan 2011]

ALDH7A1 links:

ALDH7A1 (HGNC:):

ALDH7A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-126577223-A-C is Benign according to our data. Variant chr5-126577223-A-C is described in ClinVar as [Benign]. Clinvar id is 257610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-126577223-A-C is described in Lovd as [Benign]. Variant chr5-126577223-A-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ALDH7A1	NM_001182.5 linkuse as main transcript	c.518-12T>G	intron_variant	ENST00000409134.8	NP_001173.2	P49419-1
ALDH7A1	NM_001201377.2 linkuse as main transcript	c.434-12T>G	intron_variant		NP_001188306.1	P49419-2
ALDH7A1	NM_001202404.2 linkuse as main transcript	c.518-12T>G	intron_variant		NP_001189333.2	P49419-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134.8 linkuse as main transcript	c.518-12T>G		intron_variant		1	NM_001182.5	ENSP00000387123.3		P49419-1

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5004

AN:

152154

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0707

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0196

AC:

4918

AN:

251144

Hom.:

AF XY:

0.0183

AC XY:

2488

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0715

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0520

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.00670

Gnomad NFE exome

AF:

0.0192

Gnomad OTH exome

AF:

0.0285

GnomAD4 exome

AF:

0.0199

AC:

29035

AN:

1461744

Hom.:

389

Cov.:

AF XY:

0.0194

AC XY:

14074

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0765

Gnomad4 AMR exome

AF:

0.0193

Gnomad4 ASJ exome

AF:

0.0489

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00306

Gnomad4 FIN exome

AF:

0.00687

Gnomad4 NFE exome

AF:

0.0198

Gnomad4 OTH exome

AF:

0.0236

GnomAD4 genome

AF:

0.0329

AC:

5014

AN:

152272

Hom.:

118

Cov.:

AF XY:

0.0317

AC XY:

2360

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0708

Gnomad4 AMR

AF:

0.0231

Gnomad4 ASJ

AF:

0.0487

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.0205

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0299

Hom.:

Bravo

AF:

0.0364

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pyridoxine-dependent epilepsy

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.11

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