rs6493978

Variant names:

• chr15-58033796-C-T
• rs6493978
• NM_003888.4:c.118-19515G>A

Variant summary

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

The NM_003888.4(ALDH1A2):​c.118-19515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 148,950 control chromosomes in the GnomAD database, including 16,246 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 0.46 (16246 hom., cov: 26)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 1 publications found

Genes affected

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003888.4. 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
	ALDH1A2	NM_003888.4	MANE Select	c.118-19515G>A		intron	N/A	NP_003879.2
	ALDH1A2	NM_001206897.2		c.55-19515G>A		intron	N/A	NP_001193826.1	O94788-3
	ALDH1A2	NM_170696.3		c.118-19515G>A		intron	N/A	NP_733797.1	O94788-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	ENST00000249750.9	TSL:1 MANE Select	c.118-19515G>A		intron	N/A	ENSP00000249750.4	O94788-1
	ALDH1A2	ENST00000347587.7	TSL:1	c.118-19515G>A		intron	N/A	ENSP00000309623.3	O94788-2
	ALDH1A2	ENST00000888709.1		c.118-19515G>A		intron	N/A	ENSP00000558768.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 68689 AN: 148842 Hom.: 16238 Cov.: 26

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.461 AC: 68718 AN: 148950 Hom.: 16246 Cov.: 26 AF XY: 0.458 AC XY: 33224 AN XY: 72468

African (AFR) AF: 0.392 AC: 15951 AN: 40654

American (AMR) AF: 0.416 AC: 6211 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1499 AN: 3454

East Asian (EAS) AF: 0.307 AC: 1558 AN: 5076

South Asian (SAS) AF: 0.261 AC: 1232 AN: 4718

European-Finnish (FIN) AF: 0.550 AC: 5305 AN: 9646

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35370 AN: 67174

Other (OTH) AF: 0.451 AC: 939 AN: 2084

Alfa AF: 0.492 Hom.: 2321

Bravo AF: 0.452

Asia WGS AF: 0.286 AC: 989 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.099
PhyloP100		-1.8
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: rs6493978; hg19: chr15-58325994;