15-57960760-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003888.4(ALDH1A2):c.1484+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,612,702 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (27 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.187

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=-0.82).
• BP6: Variant 15-57960760-T-G is Benign according to our data. Variant chr15-57960760-T-G is described in ClinVar as [Benign]. Clinvar id is 777462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00143 (2095/1460336) while in subpopulation AMR AF= 0.0236 (1054/44714). AF 95% confidence interval is 0.0224. There are 27 homozygotes in gnomad4_exome. There are 1185 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A2	NM_003888.4	c.1484+10A>C		intron_variant		ENST00000249750.9
ALDH1A2	NM_001206897.2	c.1421+10A>C		intron_variant
ALDH1A2	NM_170696.3	c.1370+10A>C		intron_variant
ALDH1A2	NM_170697.3	c.1196+10A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.1484+10A>C		intron_variant		1	NM_003888.4	P1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 250 AN: 152250 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00482 AC: 1209 AN: 251038 Hom.: 16 AF XY: 0.00434 AC XY: 589 AN XY: 135670

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.0248

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00957

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00143 AC: 2095 AN: 1460336 Hom.: 27 Cov.: 30 AF XY: 0.00163 AC XY: 1185 AN XY: 726628

Gnomad4 AFR exome AF: 0.000449

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.00953

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000846

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152366 Hom.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132 AN XY: 74520

Gnomad4 AFR AF: 0.000697

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000928 Hom.: 1

Bravo AF: 0.00267

Asia WGS AF: 0.00664 AC: 23 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

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.9
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs189376070; hg19: chr15-58252958;