15-57961782-CTAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003888.4(ALDH1A2):c.1251+227_1251+229del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,258 control chromosomes in the GnomAD database, including 274 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.054 (274 hom., cov: 31)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0530

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-57961782-CTAA-C is Benign according to our data. Variant chr15-57961782-CTAA-C is described in ClinVar as [Benign]. Clinvar id is 1233939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1251+227_1251+229del		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1188+227_1188+229del		intron_variant
ALDH1A2	NM_170696.3	c.1137+227_1137+229del		intron_variant
ALDH1A2	NM_170697.3	c.963+227_963+229del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1251+227_1251+229del		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8265 AN: 152140 Hom.: 273 Cov.: 31

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0594

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

GnomAD4 genome AF: 0.0543 AC: 8262 AN: 152258 Hom.: 274 Cov.: 31 AF XY: 0.0566 AC XY: 4215 AN XY: 74446

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0694

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0900

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0505 Hom.: 35

Bravo AF: 0.0529

Asia WGS AF: 0.0870 AC: 300 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs4646630; hg19: chr15-58253980;