dbSNP rs12903401: ENSG00000292375:n.352G>C (chr15-79209754-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.402

Publications

12 publications found

Variant links:

COSMIC-nc: COSV66045224

Genes affected

ENSG00000292375 (HGNC:):

ENSG00000292375 links:

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 Gene-Disease associations (from GenCC):

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

MIR184 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ANKRD34C-AS1	NR_038997.1 link	n.298-17652C>G	intron_variant	Intron 1 of 1
MIR184	NR_029705.1 link	n.-34G>C	upstream_gene_variant
MIR184	unassigned_transcript_2726	n.-86G>C	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000292375	ENST00000711326.1 link	n.352G>C	non_coding_transcript_exon_variant	Exon 1 of 2
ANKRD34C-AS1	ENST00000559225.3 link	n.470+3433C>G	intron_variant	Intron 2 of 2	4
ANKRD34C-AS1	ENST00000560872.1 link	n.178-17652C>G	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61592

AN:

151888

Hom.:

13937

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.453

AC XY:

89226

AN XY:

197054

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

3966

7933

11899

15866

19832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

710

1420

2130

2840

3550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.405

AC:

61610

AN:

152004

Hom.:

13946

Cov.:

AF XY:

0.409

AC XY:

30358

AN XY:

74306

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1777

3553

5330

7106

8883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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: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 09, 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

-0.68

CADD

Benign

6.3

(source)

DANN

Benign

0.84

PhyloP100

-0.40

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over