chr15-57960653-G-A

Position:

• chr15-57960653-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003888.4(ALDH1A2):​c.1484+117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 866,160 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (218 hom., cov: 32)
  • Exomes 𝑓: 0.013 (217 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0420

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-57960653-G-A is Benign according to our data. Variant chr15-57960653-G-A is described in ClinVar as [Benign]. Clinvar id is 1282331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.1484+117C>T		intron_variant		ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.1421+117C>T		intron_variant			NP_001193826.1
ALDH1A2	NM_170696.3	c.1370+117C>T		intron_variant			NP_733797.1
ALDH1A2	NM_170697.3	c.1196+117C>T		intron_variant			NP_733798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1484+117C>T		intron_variant		1	NM_003888.4	ENSP00000249750.4

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5441 AN: 152130 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00970

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0134 AC: 9550 AN: 713914 Hom.: 217 AF XY: 0.0123 AC XY: 4652 AN XY: 376966

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.00970

Gnomad4 EAS exome AF: 0.0386

Gnomad4 SAS exome AF: 0.00215

Gnomad4 FIN exome AF: 0.00260

Gnomad4 NFE exome AF: 0.00977

Gnomad4 OTH exome AF: 0.0185

GnomAD4 genome AF: 0.0358 AC: 5456 AN: 152246 Hom.: 218 Cov.: 32 AF XY: 0.0350 AC XY: 2609 AN XY: 74442

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0119

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00969

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0155 Hom.: 59

Bravo AF: 0.0402

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs4646634; hg19: chr15-58252851;