Genetic Variant ENST00000559225.2:n.436+3207A>G (chr15-79209980-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000559225.2(ANKRD34C-AS1):n.436+3207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 341,016 control chromosomes in the GnomAD database, including 800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 687 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 113 hom. )

Consequence

ANKRD34C-AS1
ENST00000559225.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-79209980-T-C is Benign according to our data. Variant chr15-79209980-T-C is described in ClinVar as [Benign]. Clinvar id is 1175607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ANKRD34C-AS1	NR_038997.1 link	n.298-17878A>G	intron_variant	Intron 1 of 1
MIR184	NR_029705.1 link	n.*109T>C	downstream_gene_variant
MIR184	unassigned_transcript_2726	n.*119T>C	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ANKRD34C-AS1	ENST00000559225.2 link	n.436+3207A>G	intron_variant	Intron 2 of 2	4
ANKRD34C-AS1	ENST00000560872.1 link	n.178-17878A>G	intron_variant	Intron 1 of 1	3
ANKRD34C-AS1	ENST00000661423.1 link	n.339-17878A>G	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7937

AN:

152122

Hom.:

684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.0325

GnomAD4 exome

AF:

0.00765

AC:

1445

AN:

188776

Hom.:

113

AF XY:

0.00626

AC XY:

649

AN XY:

103628

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.00898

Gnomad4 ASJ exome

AF:

0.000714

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000351

Gnomad4 FIN exome

AF:

0.0000441

Gnomad4 NFE exome

AF:

0.000494

Gnomad4 OTH exome

AF:

0.00872

GnomAD4 genome

AF:

0.0523

AC:

7960

AN:

152240

Hom.:

687

Cov.:

AF XY:

0.0502

AC XY:

3739

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.0322

Bravo

AF:

0.0592

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.15

DANN

Benign

0.60

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over