1-165681550-C-T

Variant names:

• chr1-165681550-C-T
• rs3845536
• NM_000696.4:c.592+557G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000696.4(ALDH9A1):​c.592+557G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,036 control chromosomes in the GnomAD database, including 12,427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12427 hom., cov: 33)
• Consequence: ALDH9A1 NM_000696.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 7 publications found

Genes affected

ALDH9A1 (HGNC:412): (aldehyde dehydrogenase 9 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. It has a high activity for oxidation of gamma-aminobutyraldehyde and other amino aldehydes. The enzyme catalyzes the dehydrogenation of gamma-aminobutyraldehyde to gamma-aminobutyric acid (GABA). This isozyme is a tetramer of identical 54-kD subunits. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000696.4. 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
	ALDH9A1	NM_000696.4	MANE Select	c.592+557G>A		intron	N/A	NP_000687.3
	ALDH9A1	NM_001365774.2		c.310+557G>A		intron	N/A	NP_001352703.1	P49189-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH9A1	ENST00000354775.5	TSL:1 MANE Select	c.592+557G>A		intron	N/A	ENSP00000346827.4	P49189-3
	ALDH9A1	ENST00000865475.1		c.589+560G>A		intron	N/A	ENSP00000535534.1
	ALDH9A1	ENST00000865474.1		c.562+557G>A		intron	N/A	ENSP00000535533.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60375 AN: 151918 Hom.: 12410 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60428 AN: 152036 Hom.: 12427 Cov.: 33 AF XY: 0.399 AC XY: 29633 AN XY: 74322

African (AFR) AF: 0.473 AC: 19599 AN: 41452

American (AMR) AF: 0.404 AC: 6171 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3139 AN: 5172

South Asian (SAS) AF: 0.308 AC: 1483 AN: 4822

European-Finnish (FIN) AF: 0.399 AC: 4217 AN: 10566

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23821 AN: 67972

Other (OTH) AF: 0.388 AC: 819 AN: 2112

Alfa AF: 0.371 Hom.: 14589

Bravo AF: 0.401

Asia WGS AF: 0.436 AC: 1514 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.36
DANN	Benign	0.48
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3845536; hg19: chr1-165650787;