chr15-100887320-GTCAAAAGATGACACCCAAACTGCAGTCACCTCAAAAGATGACACCCAAACTGCAGTCACC-G

Position:

• chr15-100887320-GTCAAAAGATGACACCCAAACTGCAGTCACCTCAAAAGATGACACCCAAACTGCAGTCACC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000693.4(ALDH1A3):​c.205-236_205-177del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 147,432 control chromosomes in the GnomAD database, including 65 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.023 (65 hom., cov: 32)
• Consequence: ALDH1A3 NM_000693.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.887

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 -10 ACMG points.

• BP6: Variant 15-100887320-GTCAAAAGATGACACCCAAACTGCAGTCACCTCAAAAGATGACACCCAAACTGCAGTCACC-G is Benign according to our data. Variant chr15-100887320-GTCAAAAGATGACACCCAAACTGCAGTCACCTCAAAAGATGACACCCAAACTGCAGTCACC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1216244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0226 (3338/147432) while in subpopulation NFE AF= 0.0346 (2323/67208). AF 95% confidence interval is 0.0334. There are 65 homozygotes in gnomad4. There are 1596 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A3	NM_000693.4	c.205-236_205-177del		intron_variant		ENST00000329841.10	NP_000684.2
ALDH1A3	NM_001293815.2	c.205-236_205-177del		intron_variant			NP_001280744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A3	ENST00000329841.10	c.205-236_205-177del		intron_variant		1	NM_000693.4	ENSP00000332256	P1

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3337 AN: 147344 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00640

Gnomad AMI AF: 0.0144

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.00731

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00861

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0161

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

GnomAD4 genome AF: 0.0226 AC: 3338 AN: 147432 Hom.: 65 Cov.: 32 AF XY: 0.0222 AC XY: 1596 AN XY: 71938

Gnomad4 AFR AF: 0.00638

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.00731

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00884

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.0160

Alfa AF: 0.0362 Hom.: 3

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

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1567168030; hg19: chr15-101427525;