Variant chr15-100892476-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000693.4(ALDH1A3):c.346-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,607,842 control chromosomes in the GnomAD database, including 995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 477 hom., cov: 33)

Exomes 𝑓: 0.0083 ( 518 hom. )

Consequence

ALDH1A3
NM_000693.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.50

Variant links:

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 links:

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

ALDH1A3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-100892476-T-C is Benign according to our data. Variant chr15-100892476-T-C is described in ClinVar as [Benign]. Clinvar id is 1281056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ALDH1A3	NM_000693.4 linkuse as main transcript	c.346-34T>C	intron_variant		ENST00000329841.10
ALDH1A3-AS1	NR_135827.1 linkuse as main transcript	n.4071A>G	non_coding_transcript_exon_variant	2/2
ALDH1A3	NM_001293815.2 linkuse as main transcript	c.346-3457T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10 linkuse as main transcript	c.346-34T>C		intron_variant		1	NM_000693.4	P1
ALDH1A3-AS1	ENST00000656756.1 linkuse as main transcript	n.4179A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0475

AC:

7234

AN:

152158

Hom.:

477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.0248

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0178

AC:

4358

AN:

245346

Hom.:

201

AF XY:

0.0148

AC XY:

1967

AN XY:

132580

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.00880

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.0108

Gnomad SAS exome

AF:

0.00748

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.00302

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.00830

AC:

12077

AN:

1455566

Hom.:

518

Cov.:

AF XY:

0.00787

AC XY:

5697

AN XY:

723972

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.00968

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.0423

Gnomad4 SAS exome

AF:

0.00812

Gnomad4 FIN exome

AF:

0.0240

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0477

AC:

7256

AN:

152276

Hom.:

477

Cov.:

AF XY:

0.0472

AC XY:

3512

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.0235

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.0248

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0353

Hom.:

Bravo

AF:

0.0520

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 22, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.27

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over