X-153942092-A-G

Position:

• chrX-153942092-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002910.6(RENBP):​c.688-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 930,495 control chromosomes in the GnomAD database, including 36,362 homozygotes. There are 80,029 hemizygotes in GnomAD. 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 0.38 (8090 hom., 11956 hem., cov: 21)
  • Exomes 𝑓: 0.27 (28272 hom. 68073 hem.)
• Consequence: RENBP NM_002910.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RENBP	NM_002910.6	c.688-61T>C		intron_variant		ENST00000393700.8	NP_002901.2
RENBP	XM_017029698.2	c.658-61T>C		intron_variant			XP_016885187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RENBP	ENST00000393700.8	c.688-61T>C		intron_variant		1	NM_002910.6	ENSP00000377303.3
RENBP	ENST00000369997.7	c.646-61T>C		intron_variant		5		ENSP00000359014.3
RENBP	ENST00000423624.5	n.*509-61T>C		intron_variant		5		ENSP00000394220.1
RENBP	ENST00000442361.1	n.403-439T>C		intron_variant		3		ENSP00000399278.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 41744 AN: 108865 Hom.: 8081 Cov.: 21 AF XY: 0.382 AC XY: 11918 AN XY: 31237

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.0696

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.267 AC: 219605 AN: 821587 Hom.: 28272 Cov.: 13 AF XY: 0.319 AC XY: 68073 AN XY: 213529

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.755

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.384 AC: 41795 AN: 108908 Hom.: 8090 Cov.: 21 AF XY: 0.382 AC XY: 11956 AN XY: 31290

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.420

Alfa AF: 0.300 Hom.: 2572

Bravo AF: 0.426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2269372; hg19: chrX-153207545; COSMIC: COSV64169783; COSMIC: COSV64169783;