X-153935840-G-C

Variant names:

• chrX-153935840-G-C
• rs5945377
• NM_002910.6:c.1078-264C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002910.6(RENBP):​c.1078-264C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 112,461 control chromosomes in the GnomAD database, including 5,894 homozygotes. There are 11,449 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 0.32 (5894 hom., 11449 hem., cov: 25)
• Consequence: RENBP NM_002910.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RENBP	NM_002910.6	c.1078-264C>G		intron_variant	Intron 9 of 10	ENST00000393700.8	NP_002901.2
RENBP	XM_017029698.2	c.1048-264C>G		intron_variant	Intron 9 of 10		XP_016885187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RENBP	ENST00000393700.8	c.1078-264C>G		intron_variant	Intron 9 of 10	1	NM_002910.6	ENSP00000377303.3

Frequencies

GnomAD3 genomes AF: 0.324 AC: 36375 AN: 112409 Hom.: 5894 Cov.: 25

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.00582

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.324 AC: 36420 AN: 112461 Hom.: 5894 Cov.: 25 AF XY: 0.330 AC XY: 11449 AN XY: 34679

African (AFR) AF: 0.594 AC: 18327 AN: 30866

American (AMR) AF: 0.434 AC: 4654 AN: 10729

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 635 AN: 2647

East Asian (EAS) AF: 0.686 AC: 2426 AN: 3537

South Asian (SAS) AF: 0.541 AC: 1514 AN: 2801

European-Finnish (FIN) AF: 0.142 AC: 885 AN: 6217

Middle Eastern (MID) AF: 0.326 AC: 70 AN: 215

European-Non Finnish (NFE) AF: 0.138 AC: 7353 AN: 53224

Other (OTH) AF: 0.359 AC: 552 AN: 1538

Alfa AF: 0.0821 Hom.: 371

Bravo AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.82
DANN	Benign	0.42
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5945377; hg19: chrX-153201293;