rs3825926

Positions:

• chr15-100905236-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
ALDH1A3	NM_000693.4	c.1069-287C>T		intron_variant		ENST00000329841.10
ALDH1A3-AS1	NR_135827.1	n.481-9170G>A		intron_variant, non_coding_transcript_variant
ALDH1A3	NM_001293815.2	c.748-287C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.1069-287C>T		intron_variant		1	NM_000693.4	P1
ALDH1A3-AS1	ENST00000656756.1	n.589-9170G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.00370

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0668

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0194 Hom.: 55

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.25

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: rs3825926; hg19: chr15-101445441;