Genetic Variant ENST00000561599.2:n.279C>A (chr16-83807556-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000561599.2(CDH13-AS2):n.279C>A 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 0.342 in 154,436 control chromosomes in the GnomAD database, including 9,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9163 hom., cov: 32)

Exomes 𝑓: 0.33 ( 163 hom. )

Consequence

CDH13-AS2
ENST00000561599.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0410

Publications

2 publications found

Variant links:

Genes affected

CDH13-AS2 (HGNC:56243): (CDH13 antisense RNA 2)

CDH13-AS2 links:

HSBP1 (HGNC:5203): (heat shock factor binding protein 1) The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein 1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response. [provided by RefSeq, Jul 2008]

HSBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDH13-AS2	ENST00000561599.2 link	n.279C>A	non_coding_transcript_exon_variant	Exon 1 of 5	4
CDH13-AS2	ENST00000743018.1 link	n.279C>A	non_coding_transcript_exon_variant	Exon 1 of 4
CDH13-AS2	ENST00000743019.1 link	n.275C>A	non_coding_transcript_exon_variant	Exon 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51932

AN:

151900

Hom.:

9156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.329

AC:

796

AN:

2418

Hom.:

163

Cov.:

AF XY:

0.333

AC XY:

485

AN XY:

1458

show subpopulations

African (AFR)

AF:

0.156

AC:

AN:

American (AMR)

AF:

0.191

AC:

AN:

262

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

AN:

East Asian (EAS)

AF:

0.192

AC:

AN:

South Asian (SAS)

AF:

0.294

AC:

182

AN:

618

European-Finnish (FIN)

AF:

0.273

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.385

AC:

488

AN:

1266

Other (OTH)

AF:

0.286

AC:

AN:

126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.342

AC:

51970

AN:

152018

Hom.:

9163

Cov.:

AF XY:

0.334

AC XY:

24793

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.398

AC:

16501

AN:

41434

American (AMR)

AF:

0.230

AC:

3526

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1286

AN:

3464

East Asian (EAS)

AF:

0.167

AC:

864

AN:

5162

South Asian (SAS)

AF:

0.293

AC:

1417

AN:

4830

European-Finnish (FIN)

AF:

0.297

AC:

3137

AN:

10558

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

24005

AN:

67954

Other (OTH)

AF:

0.311

AC:

657

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1698

3396

5093

6791

8489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.336

Hom.:

15676

Bravo

AF:

0.339

Asia WGS

AF:

0.233

AC:

808

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

(source)

DANN

Benign

0.60

PhyloP100

-0.041

PromoterAI

-0.00030

Neutral

(source)

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

Computational scores

Splicing

Publications

Other links and lift over