rs79544459

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.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

Publications

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

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=-0.82).

BP6

Variant 5-126577223-A-C is Benign according to our data. Variant chr5-126577223-A-C is described in ClinVar as Benign. ClinVar VariationId is 257610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001182.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH7A1	NM_001182.5	MANE Select	c.518-12T>G	intron	N/A	NP_001173.2	P49419-1
ALDH7A1	NM_001201377.2		c.434-12T>G	intron	N/A	NP_001188306.1	P49419-2
ALDH7A1	NM_001202404.2		c.518-12T>G	intron	N/A	NP_001189333.2	P49419-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH7A1	ENST00000409134.8	TSL:1 MANE Select	c.518-12T>G	intron	N/A	ENSP00000387123.3	P49419-1
ALDH7A1	ENST00000636879.1	TSL:5	c.563-12T>G	intron	N/A	ENSP00000490811.1	A0A1B0GW77
ALDH7A1	ENST00000939100.1		c.518-12T>G	intron	N/A	ENSP00000609159.1

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

GnomAD2 exomes

AF:

0.0196

AC:

4918

AN:

251144

AF XY:

0.0183

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 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

African (AFR)

AF:

0.0765

AC:

2559

AN:

33472

American (AMR)

AF:

0.0193

AC:

863

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0489

AC:

1278

AN:

26128

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.00306

AC:

264

AN:

86226

European-Finnish (FIN)

AF:

0.00687

AC:

367

AN:

53416

Middle Eastern (MID)

AF:

0.0376

AC:

217

AN:

5768

European-Non Finnish (NFE)

AF:

0.0198

AC:

22058

AN:

1111950

Other (OTH)

AF:

0.0236

AC:

1426

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1442

2884

4326

5768

7210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.0329

AC:

5014

AN:

152272

Hom.:

118

Cov.:

AF XY:

0.0317

AC XY:

2360

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0708

AC:

2939

AN:

41538

American (AMR)

AF:

0.0231

AC:

354

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

169

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00290

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00659

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0205

AC:

1394

AN:

68014

Other (OTH)

AF:

0.0298

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

238

477

715

954

1192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0299

Hom.:

Bravo

AF:

0.0364

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pyridoxine-dependent epilepsy (4)

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

(source)

DANN

Benign

0.43

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over