15-100887396-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000693.4(ALDH1A3):c.205-176G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 132,126 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.021 (50 hom., cov: 31)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 15-100887396-G-C is Benign according to our data. Variant chr15-100887396-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1202224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0213 (2814/132126) while in subpopulation NFE AF= 0.0294 (1820/61878). AF 95% confidence interval is 0.0283. There are 50 homozygotes in gnomad4. There are 1352 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A3	NM_000693.4	c.205-176G>C		intron_variant		ENST00000329841.10
ALDH1A3	NM_001293815.2	c.205-176G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.205-176G>C		intron_variant		1	NM_000693.4	P1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 2811 AN: 132036 Hom.: 50 Cov.: 31

Gnomad AFR AF: 0.00852

Gnomad AMI AF: 0.0596

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00650

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0147

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

GnomAD4 genome AF: 0.0213 AC: 2814 AN: 132126 Hom.: 50 Cov.: 31 AF XY: 0.0212 AC XY: 1352 AN XY: 63794

Gnomad4 AFR AF: 0.00855

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00652

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0375

Gnomad4 NFE AF: 0.0294

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00687 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.29
Dann	Benign	0.19

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: rs28385499; hg19: chr15-101427601; COSMIC: COSV60902462; COSMIC: COSV60902462;