chr15-79209980-T-C

Variant names:

• chr15-79209980-T-C
• rs58249183
• ENST00000711326.1:n.578T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000711326.1(ENSG00000292375):​n.578T>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 0.0276 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: ENSG00000292375 ENST00000711326.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.24
• Publications: 1 publications found

Genes affected

ENSG00000292375 (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]

MIR184 Gene-Disease associations (from GenCC):

• EDICT syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000711326.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD34C-AS1	NR_038997.1		n.298-17878A>G		intron	N/A
	MIR184	NR_029705.1		n.*109T>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000292375	ENST00000711326.1		n.578T>C		non_coding_transcript_exon	Exon 1 of 2
	ANKRD34C-AS1	ENST00000559225.3	TSL:4	n.470+3207A>G		intron	N/A
	ANKRD34C-AS1	ENST00000560872.1	TSL:3	n.178-17878A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7937 AN: 152122 Hom.: 684 Cov.: 32

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

African (AFR) AF: 0.172 AC: 1127 AN: 6534

American (AMR) AF: 0.00898 AC: 191 AN: 21268

Ashkenazi Jewish (ASJ) AF: 0.000714 AC: 4 AN: 5600

East Asian (EAS) AF: 0.00 AC: 0 AN: 8182

South Asian (SAS) AF: 0.000351 AC: 13 AN: 37008

European-Finnish (FIN) AF: 0.0000441 AC: 1 AN: 22694

Middle Eastern (MID) AF: 0.00168 AC: 1 AN: 596

European-Non Finnish (NFE) AF: 0.000494 AC: 39 AN: 78984

Other (OTH) AF: 0.00872 AC: 69 AN: 7910

GnomAD4 genome AF: 0.0523 AC: 7960 AN: 152240 Hom.: 687 Cov.: 32 AF XY: 0.0502 AC XY: 3739 AN XY: 74446

African (AFR) AF: 0.182 AC: 7567 AN: 41506

American (AMR) AF: 0.0170 AC: 260 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000867 AC: 59 AN: 68016

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0592

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.60
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs58249183; hg19: chr15-79502322;