chr15-79209754-G-C

Variant names:

• chr15-79209754-G-C
• rs12903401
• ENST00000711326.1:n.352G>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.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: ENSG00000292375 ENST00000711326.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.402
• Publications: 12 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=-0.68).
• BP6: Variant 15-79209754-G-C is Benign according to our data. Variant chr15-79209754-G-C is described in ClinVar as Benign. ClinVar VariationId is 1223338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 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.298-17652C>G		intron	N/A
	MIR184	NR_029705.1		n.-34G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000292375	ENST00000711326.1		n.352G>C		non_coding_transcript_exon	Exon 1 of 2
	ANKRD34C-AS1	ENST00000559225.3	TSL:4	n.470+3433C>G		intron	N/A
	ANKRD34C-AS1	ENST00000560872.1	TSL:3	n.178-17652C>G		intron	N/A

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

GnomAD2 exomes AF: 0.464 AC: 115006 AN: 247820 AF XY: 0.462

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 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

African (AFR) AF: 0.199 AC: 1996 AN: 10020

American (AMR) AF: 0.541 AC: 19360 AN: 35810

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 5686 AN: 11194

East Asian (EAS) AF: 0.570 AC: 7091 AN: 12440

South Asian (SAS) AF: 0.366 AC: 23513 AN: 64162

European-Finnish (FIN) AF: 0.480 AC: 15126 AN: 31528

Middle Eastern (MID) AF: 0.503 AC: 1298 AN: 2582

European-Non Finnish (NFE) AF: 0.481 AC: 80384 AN: 167006

Other (OTH) AF: 0.463 AC: 6955 AN: 15014

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

African (AFR) AF: 0.196 AC: 8138 AN: 41464

American (AMR) AF: 0.527 AC: 8043 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3466

East Asian (EAS) AF: 0.553 AC: 2848 AN: 5152

South Asian (SAS) AF: 0.364 AC: 1756 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5031 AN: 10578

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32655 AN: 67942

Other (OTH) AF: 0.449 AC: 948 AN: 2112

Alfa AF: 0.445 Hom.: 2931

Bravo AF: 0.408

Asia WGS AF: 0.420 AC: 1463 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	-0.68
CADD	Benign	6.3
DANN	Benign	0.84
PhyloP100		-0.40

Splicing

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

Other links and lift over

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