15-100885655-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000693.4(ALDH1A3):c.204+300dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (9010 hom., cov: 0)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-100885655-C-CT is Benign according to our data. Variant chr15-100885655-C-CT is described in ClinVar as [Benign]. Clinvar id is 1271421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A3	NM_000693.4	c.204+300dup		intron_variant		ENST00000329841.10
ALDH1A3	NM_001293815.2	c.204+300dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.204+300dup		intron_variant		1	NM_000693.4	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 50116 AN: 138272 Hom.: 9011 Cov.: 0

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.300

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.362 AC: 50115 AN: 138280 Hom.: 9010 Cov.: 0 AF XY: 0.364 AC XY: 24280 AN XY: 66712

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.366

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

Sep 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs4646657; hg19: chr15-101425860;