rs3825926

Variant names:

• chr15-100905236-C-T
• rs3825926
• NM_000693.4:c.1069-287C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000693.4(ALDH1A3):​c.1069-287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 152,324 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.020 (51 hom., cov: 32)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268
• Publications: 7 publications found

Genes affected

ALDH1A3 (HGNC:409): (aldehyde dehydrogenase 1 family member A3) This gene encodes an aldehyde dehydrogenase enzyme that uses retinal as a substrate. Mutations in this gene have been associated with microphthalmia, isolated 8, and expression changes have also been detected in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ALDH1A3-AS1 (HGNC:55416): (ALDH1A3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-100905236-C-T is Benign according to our data. Variant chr15-100905236-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1189283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.1069-287C>T		intron_variant	Intron 9 of 12	ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.748-287C>T		intron_variant	Intron 6 of 9		NP_001280744.1
ALDH1A3-AS1	NR_135827.1	n.481-9170G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1069-287C>T		intron_variant	Intron 9 of 12	1	NM_000693.4	ENSP00000332256.5

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3109 AN: 152206 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00372

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.0490

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0204 AC: 3105 AN: 152324 Hom.: 51 Cov.: 32 AF XY: 0.0228 AC XY: 1696 AN XY: 74486

African (AFR) AF: 0.00370 AC: 154 AN: 41574

American (AMR) AF: 0.0255 AC: 390 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.0668 AC: 346 AN: 5178

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4828

European-Finnish (FIN) AF: 0.0518 AC: 550 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0169 AC: 1151 AN: 68034

Other (OTH) AF: 0.0274 AC: 58 AN: 2114

Alfa AF: 0.0188 Hom.: 59

Bravo AF: 0.0170

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.25
PhyloP100		-0.27
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: rs3825926; hg19: chr15-101445441;