rs141536472

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_000693.4(ALDH1A3):​c.807G>A​(p.Ala269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,614,096 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000077 ( 1 hom. )

Consequence

ALDH1A3
NM_000693.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.306
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-AS1 (HGNC:55416): (ALDH1A3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 15-100898109-G-A is Benign according to our data. Variant chr15-100898109-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256762.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-100898109-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.306 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000788 (120/152330) while in subpopulation AFR AF= 0.00262 (109/41574). AF 95% confidence interval is 0.00222. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALDH1A3NM_000693.4 linkuse as main transcriptc.807G>A p.Ala269= synonymous_variant 8/13 ENST00000329841.10
ALDH1A3-AS1NR_135827.1 linkuse as main transcriptn.481-2043C>T intron_variant, non_coding_transcript_variant
ALDH1A3NM_001293815.2 linkuse as main transcriptc.486G>A p.Ala162= synonymous_variant 5/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH1A3ENST00000329841.10 linkuse as main transcriptc.807G>A p.Ala269= synonymous_variant 8/131 NM_000693.4 P1
ALDH1A3-AS1ENST00000656756.1 linkuse as main transcriptn.589-2043C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.000762
AC:
116
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00256
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000199
AC:
50
AN:
251278
Hom.:
0
AF XY:
0.000199
AC XY:
27
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.00265
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000773
AC:
113
AN:
1461766
Hom.:
1
Cov.:
30
AF XY:
0.0000811
AC XY:
59
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00236
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000788
AC:
120
AN:
152330
Hom.:
0
Cov.:
33
AF XY:
0.000792
AC XY:
59
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00262
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000523
Hom.:
0
Bravo
AF:
0.000824
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
12
DANN
Benign
0.89

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

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

Other links and lift over

dbSNP: rs141536472; hg19: chr15-101438314; COSMIC: COSV100320232; COSMIC: COSV100320232; API