Variant X-153935586-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002910.6(RENBP):c.1078-10G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,196,309 control chromosomes in the GnomAD database, including 17 homozygotes. There are 362 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., 36 hem., cov: 25)

Exomes 𝑓: 0.0011 ( 16 hom. 326 hem. )

Consequence

RENBP
NM_002910.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001877

Clinical Significance

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

Conservation

PhyloP100: -0.222

Variant links:

Genes affected

RENBP (HGNC:9959): (renin binding protein) The gene product inhibits renin activity by forming a dimer with renin, a complex known as high molecular weight renin. The encoded protein contains a leucine zipper domain, which is essential for its dimerization with renin. The gene product can catalyze the interconversion of N-acetylglucosamine to N-acetylmannosamine, indicating that it is a GlcNAc 2-epimerase. Transcript variants utilizing alternative promoters have been described in the literature. [provided by RefSeq, Jul 2008]

RENBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-153935586-C-A is Benign according to our data. Variant chrX-153935586-C-A is described in ClinVar as [Benign]. Clinvar id is 785000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00114 (1238/1083305) while in subpopulation AMR AF= 0.0238 (836/35142). AF 95% confidence interval is 0.0225. There are 16 homozygotes in gnomad4_exome. There are 326 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RENBP	NM_002910.6 linkuse as main transcript	c.1078-10G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000393700.8	NP_002901.2
RENBP	XM_017029698.2 linkuse as main transcript	c.1048-10G>T		splice_polypyrimidine_tract_variant, intron_variant			XP_016885187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RENBP	ENST00000393700.8 linkuse as main transcript	c.1078-10G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002910.6	ENSP00000377303	P1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

143

AN:

112951

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

35093

show subpopulations

Gnomad AFR

AF:

0.0000642

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000358

Gnomad FIN

AF:

0.000319

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000451

Gnomad OTH

AF:

0.00198

GnomAD3 exomes

AF:

0.00435

AC:

779

AN:

178971

Hom.:

AF XY:

0.00275

AC XY:

181

AN XY:

65883

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0257

Gnomad ASJ exome

AF:

0.000272

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000375

Gnomad NFE exome

AF:

0.000633

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00114

AC:

1238

AN:

1083305

Hom.:

Cov.:

AF XY:

0.000932

AC XY:

326

AN XY:

349735

show subpopulations

Gnomad4 AFR exome

AF:

0.0000766

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.000415

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000558

Gnomad4 FIN exome

AF:

0.000379

Gnomad4 NFE exome

AF:

0.000366

Gnomad4 OTH exome

AF:

0.000943

GnomAD4 genome

AF:

0.00127

AC:

143

AN:

113004

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

35156

show subpopulations

Gnomad4 AFR

AF:

0.0000640

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000359

Gnomad4 FIN

AF:

0.000319

Gnomad4 NFE

AF:

0.000451

Gnomad4 OTH

AF:

0.00196

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00230

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over