Genetic Variant ANKRD34C-AS1:n.436+3409A>G (chr15-79209778-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000560872.1(ANKRD34C-AS1):n.178-17676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 514,464 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 5 hom. )

Consequence

ANKRD34C-AS1
ENST00000560872.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 15-79209778-T-C is Benign according to our data. Variant chr15-79209778-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1219828.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00852 (1298/152304) while in subpopulation AFR AF= 0.0299 (1244/41564). AF 95% confidence interval is 0.0285. There are 21 homozygotes in gnomad4. There are 623 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00848

AC:

1290

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00234

AC:

585

AN:

250270

Hom.:

AF XY:

0.00159

AC XY:

216

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00115

AC:

417

AN:

362160

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

164

AN XY:

205756

show subpopulations

Gnomad4 AFR exome

AF:

0.0296

Gnomad4 AMR exome

AF:

0.00147

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000770

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00852

AC:

1298

AN:

152304

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

623

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0299

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.000339

Hom.:

Bravo

AF:

0.00989

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 14, 2019

GeneDx

Significance: Likely 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

-0.68

CADD

Benign

6.8

DANN

Benign

0.82

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