15-100879582-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The XM_047433433.1(LOC124903575):c.222C>T(p.Cys74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 148,182 control chromosomes in the GnomAD database, including 514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (513 hom., cov: 33)
  • Exomes 𝑓: 0.023 (1 hom.)
• Consequence: LOC124903575 XM_047433433.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.917

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-100879582-G-A is Benign according to our data. Variant chr15-100879582-G-A is described in ClinVar as [Benign]. Clinvar id is 1242902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.917 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903575	XM_047433433.1	c.222C>T	p.Cys74=	synonymous_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A3	ENST00000561338.5	c.15+1717G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 7886 AN: 147732 Hom.: 509 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00442

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00635

Gnomad OTH AF: 0.0403

GnomAD4 exome AF: 0.0234 AC: 8 AN: 342 Hom.: 1 Cov.: 0 AF XY: 0.0236 AC XY: 5 AN XY: 212

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0769

Gnomad4 NFE exome AF: 0.00769

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0535 AC: 7904 AN: 147840 Hom.: 513 Cov.: 33 AF XY: 0.0558 AC XY: 4020 AN XY: 72008

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00442

Gnomad4 EAS AF: 0.0486

Gnomad4 SAS AF: 0.0497

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0348 Hom.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.1
Dann	Benign	0.81

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: rs143452518; hg19: chr15-101419787;