Genetic Variant NM_006913.4:c.140+64C>A (chr6-32178715-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006913.4(RNF5):c.140+64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,507,000 control chromosomes in the GnomAD database, including 33,346 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 0.18 ( 2642 hom., cov: 31)

Exomes 𝑓: 0.20 ( 30704 hom. )

Consequence

RNF5
NM_006913.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.576

Publications

57 publications found

Variant links:

Genes affected

RNF5 (HGNC:10068): (ring finger protein 5) The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions. [provided by RefSeq, Jul 2008]

RNF5 links:

Genome browser will be placed here

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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF5	NM_006913.4 link	c.140+64C>A		intron_variant	Intron 1 of 5	ENST00000375094.4	NP_008844.1	Q99942A0A024RCQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF5	ENST00000375094.4 link	c.140+64C>A		intron_variant	Intron 1 of 5	1	NM_006913.4	ENSP00000364235.3		Q99942
RNF5	ENST00000487940.1 link	n.215+64C>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27518

AN:

151776

Hom.:

2645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.0430

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.203

AC:

275264

AN:

1355106

Hom.:

30704

AF XY:

0.200

AC XY:

135360

AN XY:

677718

show subpopulations

African (AFR)

AF:

0.193

AC:

5999

AN:

31008

American (AMR)

AF:

0.0937

AC:

3852

AN:

41110

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3673

AN:

24482

East Asian (EAS)

AF:

0.0235

AC:

906

AN:

38570

South Asian (SAS)

AF:

0.136

AC:

11215

AN:

82270

European-Finnish (FIN)

AF:

0.142

AC:

5697

AN:

40172

Middle Eastern (MID)

AF:

0.0917

AC:

505

AN:

5508

European-Non Finnish (NFE)

AF:

0.224

AC:

232219

AN:

1035090

Other (OTH)

AF:

0.197

AC:

11198

AN:

56896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10132

20264

30397

40529

50661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7932

15864

23796

31728

39660

<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:

0.181

AC:

27513

AN:

151894

Hom.:

2642

Cov.:

AF XY:

0.174

AC XY:

12926

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.187

AC:

7761

AN:

41410

American (AMR)

AF:

0.118

AC:

1809

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

509

AN:

3464

East Asian (EAS)

AF:

0.0431

AC:

223

AN:

5172

South Asian (SAS)

AF:

0.159

AC:

764

AN:

4808

European-Finnish (FIN)

AF:

0.141

AC:

1482

AN:

10518

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14362

AN:

67936

Other (OTH)

AF:

0.168

AC:

355

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1132

2264

3395

4527

5659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.201

Hom.:

10817

Bravo

AF:

0.182

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.7

(source)

DANN

Benign

0.61

PhyloP100

-0.58

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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