15-57961980-T-A

Variant names:

• chr15-57961980-T-A
• rs35153668
• NM_003888.4:c.1251+32A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003888.4(ALDH1A2):​c.1251+32A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,613,580 control chromosomes in the GnomAD database, including 457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (208 hom., cov: 32)
  • Exomes 𝑓: 0.011 (249 hom.)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-57961980-T-A is Benign according to our data. Variant chr15-57961980-T-A is described in ClinVar as Benign. ClinVar VariationId is 1257533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 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.1251+32A>T		intron	N/A	NP_003879.2
	ALDH1A2	NM_001206897.2		c.1188+32A>T		intron	N/A	NP_001193826.1	O94788-3
	ALDH1A2	NM_170696.3		c.1137+32A>T		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.1251+32A>T		intron	N/A	ENSP00000249750.4	O94788-1
	ALDH1A2	ENST00000347587.7	TSL:1	c.1137+32A>T		intron	N/A	ENSP00000309623.3	O94788-2
	ALDH1A2	ENST00000559517.5	TSL:1	c.963+32A>T		intron	N/A	ENSP00000453408.1	O94788-4

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5026 AN: 152158 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00823

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0179 AC: 4487 AN: 251370 AF XY: 0.0158

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.0381

Gnomad ASJ exome AF: 0.00755

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.00950

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0111 AC: 16199 AN: 1461304 Hom.: 249 Cov.: 31 AF XY: 0.0108 AC XY: 7845 AN XY: 727022

African (AFR) AF: 0.0918 AC: 3073 AN: 33460

American (AMR) AF: 0.0373 AC: 1667 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00784 AC: 205 AN: 26132

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39692

South Asian (SAS) AF: 0.0109 AC: 943 AN: 86238

European-Finnish (FIN) AF: 0.00264 AC: 141 AN: 53414

Middle Eastern (MID) AF: 0.0174 AC: 100 AN: 5760

European-Non Finnish (NFE) AF: 0.00827 AC: 9187 AN: 1111504

Other (OTH) AF: 0.0143 AC: 861 AN: 60380

GnomAD4 genome AF: 0.0331 AC: 5042 AN: 152276 Hom.: 208 Cov.: 32 AF XY: 0.0327 AC XY: 2436 AN XY: 74464

African (AFR) AF: 0.0927 AC: 3853 AN: 41554

American (AMR) AF: 0.0311 AC: 475 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4818

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00822 AC: 559 AN: 68022

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.00914 Hom.: 7

Bravo AF: 0.0385

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.056
DANN	Benign	0.78
PhyloP100		-1.7
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: rs35153668; hg19: chr15-58254178;