rs2269371

Positions:

• chrX-153941572-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002910.6(RENBP):​c.851A>G​(p.Asp284Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,206,212 control chromosomes in the GnomAD database, including 700 homozygotes. There are 6,087 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 0.047 (252 hom., 1297 hem., cov: 20)
  • Exomes 𝑓: 0.014 (448 hom. 4790 hem.)
• Consequence: RENBP NM_002910.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RENBP	NM_002910.6	c.851A>G	p.Asp284Gly	missense_variant	8/11	ENST00000393700.8	NP_002901.2
RENBP	XM_017029698.2	c.821A>G	p.Asp274Gly	missense_variant	8/11		XP_016885187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RENBP	ENST00000393700.8	c.851A>G	p.Asp284Gly	missense_variant	8/11	1	NM_002910.6	ENSP00000377303	P1

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 5169 AN: 108796 Hom.: 253 Cov.: 20 AF XY: 0.0416 AC XY: 1295 AN XY: 31136

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0223

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.00384

Gnomad MID AF: 0.00851

Gnomad NFE AF: 0.00641

Gnomad OTH AF: 0.0415

GnomAD3 exomes AF: 0.0318 AC: 5812 AN: 182935 Hom.: 221 AF XY: 0.0255 AC XY: 1723 AN XY: 67663

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0936

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.0202

Gnomad SAS exome AF: 0.0255

Gnomad FIN exome AF: 0.00387

Gnomad NFE exome AF: 0.00637

Gnomad OTH exome AF: 0.0244

GnomAD4 exome AF: 0.0139 AC: 15230 AN: 1097368 Hom.: 448 Cov.: 31 AF XY: 0.0132 AC XY: 4790 AN XY: 362836

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0862

Gnomad4 ASJ exome AF: 0.00480

Gnomad4 EAS exome AF: 0.0325

Gnomad4 SAS exome AF: 0.0270

Gnomad4 FIN exome AF: 0.00323

Gnomad4 NFE exome AF: 0.00547

Gnomad4 OTH exome AF: 0.0203

GnomAD4 genome AF: 0.0475 AC: 5167 AN: 108844 Hom.: 252 Cov.: 20 AF XY: 0.0416 AC XY: 1297 AN XY: 31194

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.0265

Gnomad4 SAS AF: 0.0281

Gnomad4 FIN AF: 0.00384

Gnomad4 NFE AF: 0.00641

Gnomad4 OTH AF: 0.0410

Alfa AF: 0.0324 Hom.: 326

Bravo AF: 0.0562

ESP6500AA AF: 0.127 AC: 488

ESP6500EA AF: 0.00550 AC: 37

ExAC AF: 0.0307 AC: 3723

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	0.071	P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.028	D;D
Polyphen		0.12	B;.
Vest4		0.17
MPC		0.63
ClinPred		0.034	T
GERP RS		5.2
Varity_R		0.39
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2269371; hg19: chrX-153207025; COSMIC: COSV64170286; COSMIC: COSV64170286;