chr8-143383748-C-T

Variant names:

• chr8-143383748-C-T
• rs11785598
• NM_052924.3:c.*1097C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_052924.3(RHPN1):​c.*1097C>T variant causes a 3 prime UTR 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 NM_052924.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• 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	c.*1097C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000289013.11	NP_443156.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3552 AN: 152174 Hom.: 55 Cov.: 33

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: 2 AN: 46 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 2 AN XY: 36

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0455

GnomAD4 genome AF: 0.0233 AC: 3552 AN: 152292 Hom.: 55 Cov.: 33 AF XY: 0.0227 AC XY: 1691 AN XY: 74476

Gnomad4 AFR AF: 0.00693

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0305 Hom.: 21

Bravo AF: 0.0241

Asia WGS AF: 0.00347 AC: 13 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
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs11785598; hg19: chr8-144465918;