15-100887380-C-G

Position:

• chr15-100887380-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000693.4(ALDH1A3):​c.205-192C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (5 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.58

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-100887380-C-G is Benign according to our data. Variant chr15-100887380-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1199990.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.205-192C>G		intron_variant		ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.205-192C>G		intron_variant			NP_001280744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.205-192C>G		intron_variant		1	NM_000693.4	ENSP00000332256	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 607 AN: 139150 Hom.: 5 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00122

Gnomad AMI AF: 0.00228

Gnomad AMR AF: 0.00346

Gnomad ASJ AF: 0.00206

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00374

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.00676

Gnomad OTH AF: 0.00413

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00435 AC: 606 AN: 139236 Hom.: 5 Cov.: 32 AF XY: 0.00452 AC XY: 307 AN XY: 67852

Gnomad4 AFR AF: 0.00122

Gnomad4 AMR AF: 0.00345

Gnomad4 ASJ AF: 0.00206

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00734

Gnomad4 NFE AF: 0.00676

Gnomad4 OTH AF: 0.00410

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

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.33
DANN	Benign	0.27

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: rs28673034; hg19: chr15-101427585;