rs12903401

chr15-79209754-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000711326.1(ENSG00000292375):n.352G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 501,760 control chromosomes in the GnomAD database, including 52,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13946 hom., cov: 32)
  • Exomes 𝑓: 0.46 (38652 hom.)
• Consequence: ENST00000711326.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.402

Genes affected

(HGNC:):

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

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 15-79209754-G-C is Benign according to our data. Variant chr15-79209754-G-C is described in ClinVar as [Benign]. Clinvar id is 1223338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD34C-AS1	NR_038997.1	n.298-17652C>G		intron_variant, non_coding_transcript_variant
MIR184	NR_029705.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000711326.1	n.352G>C		non_coding_transcript_exon_variant	1/2
ANKRD34C-AS1	ENST00000685737.1	n.316+73895C>G		intron_variant, non_coding_transcript_variant
MIR184	ENST00000384962.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61592 AN: 151888 Hom.: 13937 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.450

GnomAD3 exomes AF: 0.464 AC: 115006 AN: 247820 Hom.: 27733 AF XY: 0.462 AC XY: 61934 AN XY: 134128

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.542

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.566

Gnomad SAS exome AF: 0.358

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.461 AC: 161409 AN: 349756 Hom.: 38652 Cov.: 0 AF XY: 0.453 AC XY: 89226 AN XY: 197054

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.405 AC: 61610 AN: 152004 Hom.: 13946 Cov.: 32 AF XY: 0.409 AC XY: 30358 AN XY: 74306

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.449

Alfa AF: 0.445 Hom.: 2931

Bravo AF: 0.408

Asia WGS AF: 0.420 AC: 1463 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	6.3
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12903401; hg19: chr15-79502096; COSMIC: COSV66045224;