Variant chr15-100895882-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000693.4(ALDH1A3):c.667-51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,481,986 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 20 hom. )

Consequence

ALDH1A3
NM_000693.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.30

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=-0.84).

BP6

Variant 15-100895882-G-A is Benign according to our data. Variant chr15-100895882-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1218898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00996 (1517/152354) while in subpopulation AFR AF= 0.0334 (1390/41592). AF 95% confidence interval is 0.032. There are 25 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ALDH1A3	NM_000693.4 linkuse as main transcript	c.667-51G>A	intron_variant		ENST00000329841.10
ALDH1A3-AS1	NR_135827.1 linkuse as main transcript	n.665C>T	non_coding_transcript_exon_variant	2/2
ALDH1A3	NM_001293815.2 linkuse as main transcript	c.346-51G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10 linkuse as main transcript	c.667-51G>A		intron_variant		1	NM_000693.4	P1
ALDH1A3-AS1	ENST00000656756.1 linkuse as main transcript	n.773C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00983

AC:

1497

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00549

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00326

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00250

AC:

475

AN:

189998

Hom.:

AF XY:

0.00189

AC XY:

193

AN XY:

101988

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.00239

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000446

Gnomad SAS exome

AF:

0.000810

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000198

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.00135

AC:

1792

AN:

1329632

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

808

AN XY:

663548

show subpopulations

Gnomad4 AFR exome

AF:

0.0335

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00653

Gnomad4 SAS exome

AF:

0.000532

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.000179

Gnomad4 OTH exome

AF:

0.00339

GnomAD4 genome

AF:

0.00996

AC:

1517

AN:

152354

Hom.:

Cov.:

AF XY:

0.00960

AC XY:

715

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0334

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00327

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00412

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.19

DANN

Benign

0.70

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