15-100879640-G-A

Position:

• chr15-100879640-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XM_047433433.1(LOC124903575):​c.164C>T​(p.Pro55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 171,528 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (468 hom., cov: 33)
  • Exomes 𝑓: 0.028 (27 hom.)
• Consequence: LOC124903575 XM_047433433.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.262

Genes affected

LOC124903575 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-100879640-G-A is Benign according to our data. Variant chr15-100879640-G-A is described in ClinVar as [Benign]. Clinvar id is 1243882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903575	XM_047433433.1	c.164C>T	p.Pro55Leu	missense_variant	1/1		XP_047289389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000561338.5	c.15+1775G>A		intron_variant		4		ENSP00000452789

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 7997 AN: 148412 Hom.: 466 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.00498

Gnomad EAS AF: 0.0460

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00645

Gnomad OTH AF: 0.0385

GnomAD4 exome AF: 0.0283 AC: 652 AN: 23008 Hom.: 27 Cov.: 0 AF XY: 0.0252 AC XY: 308 AN XY: 12228

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.0557

Gnomad4 SAS exome AF: 0.0756

Gnomad4 FIN exome AF: 0.0876

Gnomad4 NFE exome AF: 0.00826

Gnomad4 OTH exome AF: 0.0327

GnomAD4 genome AF: 0.0540 AC: 8015 AN: 148520 Hom.: 468 Cov.: 33 AF XY: 0.0571 AC XY: 4136 AN XY: 72380

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.00498

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.00645

Gnomad4 OTH AF: 0.0381

Alfa AF: 0.0346 Hom.: 34

Bravo AF: 0.0529

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.85

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: rs181001592; hg19: chr15-101419845;