dbSNP rs146438406: ALDH7A1:p.Arg81Arg (chr5-126593354-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_001182.5(ALDH7A1):c.243A>G(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,598,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

ALDH7A1
NM_001182.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.171

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 5-126593354-T-C is Benign according to our data. Variant chr5-126593354-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.171 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000879 (123/139898) while in subpopulation AFR AF = 0.00319 (114/35696). AF 95% confidence interval is 0.00272. There are 0 homozygotes in GnomAd4. There are 69 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDH7A1	NM_001182.5	MANE Select	c.243A>G	p.Arg81Arg	synonymous	Exon 2 of 18	NP_001173.2	P49419-1
ALDH7A1	NM_001201377.2		c.159A>G	p.Arg53Arg	synonymous	Exon 2 of 18	NP_001188306.1	P49419-2
ALDH7A1	NM_001202404.2		c.243A>G	p.Arg81Arg	synonymous	Exon 2 of 16	NP_001189333.2	P49419-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDH7A1	ENST00000409134.8	TSL:1 MANE Select	c.243A>G	p.Arg81Arg	synonymous	Exon 2 of 18	ENSP00000387123.3	P49419-1
ALDH7A1	ENST00000636879.1	TSL:5	c.243A>G	p.Arg81Arg	synonymous	Exon 2 of 19	ENSP00000490811.1	A0A1B0GW77
ALDH7A1	ENST00000939100.1		c.243A>G	p.Arg81Arg	synonymous	Exon 2 of 19	ENSP00000609159.1

Frequencies

GnomAD3 genomes

AF:

0.000880

AC:

123

AN:

139786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000495

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00104

GnomAD2 exomes

AF:

0.000230

AC:

AN:

247386

AF XY:

0.000194

show subpopulations

Gnomad AFR exome

AF:

0.00335

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.0000816

AC:

119

AN:

1458108

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

AN XY:

725400

show subpopulations

African (AFR)

AF:

0.00292

AC:

AN:

33212

American (AMR)

AF:

0.0000673

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5254

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110108

Other (OTH)

AF:

0.000249

AC:

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000879

AC:

123

AN:

139898

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

68324

show subpopulations

African (AFR)

AF:

0.00319

AC:

114

AN:

35696

American (AMR)

AF:

0.000494

AC:

AN:

14162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3312

East Asian (EAS)

AF:

0.00

AC:

AN:

4780

South Asian (SAS)

AF:

0.00

AC:

AN:

4406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64424

Other (OTH)

AF:

0.00103

AC:

AN:

1942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000614

Hom.:

Bravo

AF:

0.00105

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pyridoxine-dependent epilepsy (3)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.3

(source)

DANN

Benign

0.73

PhyloP100

-0.17

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

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