Genetic Variant RHPN1:n.3186C>T (chr8-143383748-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000522335.5(RHPN1):n.3186C>T 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 0.0233 in 152,338 control chromosomes in the GnomAD database, including 55 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 0.023 ( 55 hom., cov: 33)

Exomes 𝑓: 0.043 ( 0 hom. )

Consequence

RHPN1
ENST00000522335.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.504

Publications

4 publications found

Variant links:

Genes affected

RHPN1 (HGNC:19973): (rhophilin Rho GTPase binding protein 1) Predicted to be involved in signal transduction. Predicted to act upstream of or within several processes, including focal adhesion assembly; glomerular filtration; and negative regulation of stress fiber assembly. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHPN1 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=-0.8).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0233 (3552/152292) while in subpopulation NFE AF = 0.0353 (2403/68000). AF 95% confidence interval is 0.0342. There are 55 homozygotes in GnomAd4. There are 1691 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHPN1	NM_052924.3 link	c.*1097C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000289013.11	NP_443156.2	Q8TCX5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHPN1	ENST00000522335.5 link	n.3186C>T	non_coding_transcript_exon_variant	Exon 14 of 14	1
RHPN1	ENST00000289013.11 link	c.*1097C>T	3_prime_UTR_variant	Exon 15 of 15	1	NM_052924.3	ENSP00000289013.6	Q8TCX5
RHPN1	ENST00000715591.1 link	c.*1326C>T	3_prime_UTR_variant	Exon 14 of 14			ENSP00000520485.1

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3552

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00695

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.0296

GnomAD4 exome

AF:

0.0435

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0556

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0455

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0233

AC:

3552

AN:

152292

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1691

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00693

AC:

288

AN:

41566

American (AMR)

AF:

0.0335

AC:

513

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00705

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0182

AC:

193

AN:

10630

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0353

AC:

2403

AN:

68000

Other (OTH)

AF:

0.0293

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

193

386

578

771

964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0311

Hom.:

Bravo

AF:

0.0241

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.5

(source)

DANN

Benign

0.63

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over