15-100885498-T-C

Position:

• chr15-100885498-T-C

Variant summary

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

The NM_000693.4(ALDH1A3):​c.204+127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 644,068 control chromosomes in the GnomAD database, including 36,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (13422 hom., cov: 32)
  • Exomes 𝑓: 0.27 (23063 hom.)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-100885498-T-C is Benign according to our data. Variant chr15-100885498-T-C is described in ClinVar as [Benign]. Clinvar id is 683870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.204+127T>C		intron_variant		ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.204+127T>C		intron_variant			NP_001280744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.204+127T>C		intron_variant		1	NM_000693.4	ENSP00000332256	P1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55599 AN: 152032 Hom.: 13381 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.267 AC: 131419 AN: 491918 Hom.: 23063 AF XY: 0.263 AC XY: 68770 AN XY: 261122

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.709

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.366 AC: 55703 AN: 152150 Hom.: 13422 Cov.: 32 AF XY: 0.367 AC XY: 27319 AN XY: 74408

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.332

Alfa AF: 0.234 Hom.: 6511

Bravo AF: 0.388

Asia WGS AF: 0.477 AC: 1656 AN: 3478

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	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.22

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: rs4646656; hg19: chr15-101425703; COSMIC: COSV60901185; COSMIC: COSV60901185;