rs57902950

Variant names:

• chr5-126575440-G-A
• rs57902950
• NM_001182.5:c.675C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-126575440-G-A
• chr5-126575440-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001182.5(ALDH7A1):​c.675C>T​(p.Leu225Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,613,094 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (184 hom.)
• Consequence: ALDH7A1 NM_001182.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.65
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 5-126575440-G-A is Benign according to our data. Variant chr5-126575440-G-A is described in ClinVar as Benign. ClinVar VariationId is 128349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	NM_001182.5	MANE Select	c.675C>T	p.Leu225Leu	synonymous	Exon 7 of 18	NP_001173.2	P49419-1
	ALDH7A1	NM_001201377.2		c.591C>T	p.Leu197Leu	synonymous	Exon 7 of 18	NP_001188306.1	P49419-2
	ALDH7A1	NM_001202404.2		c.675C>T	p.Leu225Leu	synonymous	Exon 7 of 16	NP_001189333.2	P49419-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH7A1	ENST00000409134.8	TSL:1 MANE Select	c.675C>T	p.Leu225Leu	synonymous	Exon 7 of 18	ENSP00000387123.3	P49419-1
	ALDH7A1	ENST00000939104.1		c.542C>T	p.Ser181Leu	missense	Exon 6 of 15	ENSP00000609163.1
	ALDH7A1	ENST00000636879.1	TSL:5	c.720C>T	p.Leu240Leu	synonymous	Exon 8 of 19	ENSP00000490811.1	A0A1B0GW77

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2791 AN: 152026 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00532

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.0130

GnomAD2 exomes AF: 0.0121 AC: 3028 AN: 250542 AF XY: 0.0120

Gnomad AFR exome AF: 0.0573

Gnomad AMR exome AF: 0.00293

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.0548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.00834

GnomAD4 exome AF: 0.00491 AC: 7177 AN: 1460950 Hom.: 184 Cov.: 30 AF XY: 0.00541 AC XY: 3929 AN XY: 726724

African (AFR) AF: 0.0567 AC: 1897 AN: 33440

American (AMR) AF: 0.00343 AC: 153 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26082

East Asian (EAS) AF: 0.0365 AC: 1446 AN: 39644

South Asian (SAS) AF: 0.0293 AC: 2521 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00661 AC: 38 AN: 5748

European-Non Finnish (NFE) AF: 0.000349 AC: 388 AN: 1111716

Other (OTH) AF: 0.0121 AC: 730 AN: 60332

GnomAD4 genome AF: 0.0184 AC: 2795 AN: 152144 Hom.: 84 Cov.: 32 AF XY: 0.0178 AC XY: 1322 AN XY: 74400

African (AFR) AF: 0.0546 AC: 2267 AN: 41534

American (AMR) AF: 0.00531 AC: 81 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.0487 AC: 253 AN: 5190

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000383 AC: 26 AN: 67956

Other (OTH) AF: 0.0133 AC: 28 AN: 2102

Alfa AF: 0.00813 Hom.: 46

Bravo AF: 0.0212

Asia WGS AF: 0.0610 AC: 210 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000890

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Pyridoxine-dependent epilepsy (3)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.1
DANN	Benign	0.73
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57902950; hg19: chr5-125911132; COSMIC: COSV107512038; COSMIC: COSV107512038;