5-126551993-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001182.5(ALDH7A1):c.1317+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,488,570 control chromosomes in the GnomAD database, including 387,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38538 hom., cov: 32)

Exomes 𝑓: 0.72 ( 348644 hom. )

Consequence

ALDH7A1
NM_001182.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.968

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

pyridoxine-dependent epilepsy
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet, ClinGen
pyridoxine-dependent epilepsy caused by ALDH7A1 mutant
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ALDH7A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 5-126551993-C-T is Benign according to our data. Variant chr5-126551993-C-T is described in ClinVar as Benign. ClinVar VariationId is 1188913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALDH7A1	NM_001182.5 link	c.1317+28G>A	intron_variant	Intron 14 of 17	ENST00000409134.8	NP_001173.2	P49419-1
ALDH7A1	NM_001201377.2 link	c.1233+28G>A	intron_variant	Intron 14 of 17		NP_001188306.1	P49419-2
ALDH7A1	NM_001202404.2 link	c.1125+28G>A	intron_variant	Intron 12 of 15		NP_001189333.2	P49419-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH7A1	ENST00000409134.8 link	c.1317+28G>A		intron_variant	Intron 14 of 17	1	NM_001182.5	ENSP00000387123.3		P49419-1

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107840

AN:

151950

Hom.:

38503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.889

Gnomad AMR

AF:

0.781

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.674

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.722

Gnomad OTH

AF:

0.698

GnomAD2 exomes

AF:

0.714

AC:

178740

AN:

250284

AF XY:

0.707

show subpopulations

Gnomad AFR exome

AF:

0.682

Gnomad AMR exome

AF:

0.823

Gnomad ASJ exome

AF:

0.660

Gnomad EAS exome

AF:

0.745

Gnomad FIN exome

AF:

0.683

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.720

AC:

962595

AN:

1336500

Hom.:

348644

Cov.:

AF XY:

0.716

AC XY:

481169

AN XY:

672036

show subpopulations

African (AFR)

AF:

0.673

AC:

20975

AN:

31148

American (AMR)

AF:

0.817

AC:

36383

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.666

AC:

16886

AN:

25352

East Asian (EAS)

AF:

0.800

AC:

31286

AN:

39086

South Asian (SAS)

AF:

0.615

AC:

51509

AN:

83756

European-Finnish (FIN)

AF:

0.676

AC:

35973

AN:

53198

Middle Eastern (MID)

AF:

0.683

AC:

2814

AN:

4122

European-Non Finnish (NFE)

AF:

0.728

AC:

727085

AN:

999096

Other (OTH)

AF:

0.706

AC:

39684

AN:

56204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

13200

26400

39599

52799

65999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17244

34488

51732

68976

86220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.710

AC:

107920

AN:

152070

Hom.:

38538

Cov.:

AF XY:

0.707

AC XY:

52567

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.677

AC:

28066

AN:

41464

American (AMR)

AF:

0.781

AC:

11932

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

2320

AN:

3468

East Asian (EAS)

AF:

0.760

AC:

3939

AN:

5186

South Asian (SAS)

AF:

0.618

AC:

2968

AN:

4802

European-Finnish (FIN)

AF:

0.674

AC:

7120

AN:

10560

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.722

AC:

49069

AN:

67994

Other (OTH)

AF:

0.703

AC:

1484

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1584

3167

4751

6334

7918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.718

Hom.:

164910

Bravo

AF:

0.720

Asia WGS

AF:

0.681

AC:

2370

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 87% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 81. Only high quality variants are reported. -

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pyridoxine-dependent epilepsy

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.9

(source)

DANN

Benign

0.73

PhyloP100

-0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over