Variant chr15-100885376-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000693.4(ALDH1A3):c.204+5A>C variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00095 in 1,587,086 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 9 hom. )

Consequence

ALDH1A3
NM_000693.4 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.0002093

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 15-100885376-A-C is Benign according to our data. Variant chr15-100885376-A-C is described in ClinVar as [Benign]. Clinvar id is 473868.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00492 (749/152342) while in subpopulation AFR AF= 0.0172 (716/41558). AF 95% confidence interval is 0.0162. There are 6 homozygotes in gnomad4. There are 330 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4 linkuse as main transcript	c.204+5A>C		splice_donor_5th_base_variant, intron_variant		ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2 linkuse as main transcript	c.204+5A>C		splice_donor_5th_base_variant, intron_variant			NP_001280744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10 linkuse as main transcript	c.204+5A>C		splice_donor_5th_base_variant, intron_variant		1	NM_000693.4	ENSP00000332256	P1

Frequencies

GnomAD3 genomes

AF:

0.00491

AC:

748

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00124

AC:

312

AN:

250964

Hom.:

AF XY:

0.000869

AC XY:

118

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000528

AC:

758

AN:

1434744

Hom.:

Cov.:

AF XY:

0.000454

AC XY:

325

AN XY:

715632

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000817

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000230

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00492

AC:

749

AN:

152342

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0172

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.00531

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Isolated microphthalmia 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.11

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

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