X-153935408-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002910.6(RENBP):c.1166-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,136,686 control chromosomes in the GnomAD database, including 78 homozygotes. There are 2,086 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (5 hom., 97 hem., cov: 24)
  • Exomes 𝑓: 0.0035 (73 hom. 1989 hem.)
• Consequence: RENBP NM_002910.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003076
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.764

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-153935408-C-T is Benign according to our data. Variant chrX-153935408-C-T is described in ClinVar as [Benign]. Clinvar id is 723213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RENBP	NM_002910.6	c.1166-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000393700.8
RENBP	XM_017029698.2	c.1136-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RENBP	ENST00000393700.8	c.1166-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002910.6	P1

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 197 AN: 111872 Hom.: 6 Cov.: 24 AF XY: 0.00285 AC XY: 97 AN XY: 34070

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000283

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00693 AC: 917 AN: 132251 Hom.: 36 AF XY: 0.0109 AC XY: 425 AN XY: 39111

Gnomad AFR exome AF: 0.0000996

Gnomad AMR exome AF: 0.0000498

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000907

Gnomad SAS exome AF: 0.0770

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000170

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00350 AC: 3587 AN: 1024765 Hom.: 73 Cov.: 26 AF XY: 0.00637 AC XY: 1989 AN XY: 312371

Gnomad4 AFR exome AF: 0.000124

Gnomad4 AMR exome AF: 0.0000352

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.0709

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000415

Gnomad4 OTH exome AF: 0.00404

GnomAD4 genome AF: 0.00173 AC: 194 AN: 111921 Hom.: 5 Cov.: 24 AF XY: 0.00284 AC XY: 97 AN XY: 34129

Gnomad4 AFR AF: 0.0000323

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000284

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000740 Hom.: 6

Bravo AF: 0.000400

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 05, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.2
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.0020
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: rs371634111; hg19: chrX-153200861;