15-57960536-C-T

Position:

• chr15-57960536-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003888.4(ALDH1A2):​c.1484+234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 152,182 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.032 (190 hom., cov: 32)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0480

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-57960536-C-T is Benign according to our data. Variant chr15-57960536-C-T is described in ClinVar as [Benign]. Clinvar id is 1283631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1484+234G>A		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1421+234G>A		intron_variant
ALDH1A2	NM_170696.3	c.1370+234G>A		intron_variant
ALDH1A2	NM_170697.3	c.1196+234G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1484+234G>A		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4885 AN: 152064 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00812

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0322 AC: 4902 AN: 152182 Hom.: 190 Cov.: 32 AF XY: 0.0319 AC XY: 2371 AN XY: 74398

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00810

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0304 Hom.: 27

Bravo AF: 0.0372

Asia WGS AF: 0.0240 AC: 83 AN: 3476

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.36

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: rs34682734; hg19: chr15-58252734;