Genetic Variant ENST00000559225.2:n.436+3409A>T (chr15-79209778-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000559225.2(ANKRD34C-AS1):n.436+3409A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 514,464 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 11 hom. )

Consequence

ANKRD34C-AS1
ENST00000559225.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Variant links:

Genes affected

ANKRD34C-AS1 (HGNC:48618): (ANKRD34C antisense RNA 1)

ANKRD34C-AS1 links:

MIR184 (HGNC:31555): (microRNA 184) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of target mRNAs. This microRNA represents the most abundant miRNA in the corneal and lens epithelia of the eye and has been shown to interfere with target binding by another miRNA, miR-205. Through regulation of the VEGF and Akt signaling pathways, this microRNA may inhibit corneal angiogenesis. Mutations in the seed region of this microRNA cause familial keratoconus with cataract, also known as EDICT syndrome. [provided by RefSeq, Mar 2017]

MIR184 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BS2

High Homozygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ANKRD34C-AS1	NR_038997.1 link	n.298-17676A>T	intron_variant	Intron 1 of 1
MIR184	NR_029705.1 link	n.-10T>A	upstream_gene_variant
MIR184	unassigned_transcript_2726	n.-62T>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ANKRD34C-AS1	ENST00000559225.2 link	n.436+3409A>T	intron_variant	Intron 2 of 2	4
ANKRD34C-AS1	ENST00000560872.1 link	n.178-17676A>T	intron_variant	Intron 1 of 1	3
ANKRD34C-AS1	ENST00000661423.1 link	n.339-17676A>T	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000943

AC:

236

AN:

250270

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00734

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.00134

AC:

485

AN:

362156

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

404

AN XY:

205752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00710

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000510

Gnomad4 OTH exome

AF:

0.000899

GnomAD4 genome

AF:

0.000210

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000424

Hom.:

Bravo

AF:

0.0000642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.3

DANN

Benign

0.91

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over