rs2269371

Variant names:

• chrX-153941572-T-C
• rs2269371
• NM_002910.6:c.851A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002910.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RENBP	NM_002910.6	MANE Select	c.851A>G	p.Asp284Gly	missense	Exon 8 of 11	NP_002901.2	P51606-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RENBP	ENST00000393700.8	TSL:1 MANE Select	c.851A>G	p.Asp284Gly	missense	Exon 8 of 11	ENSP00000377303.3	P51606-1
	RENBP	ENST00000875215.1		c.851A>G	p.Asp284Gly	missense	Exon 8 of 12	ENSP00000545274.1
	RENBP	ENST00000369997.7	TSL:5	c.809A>G	p.Asp270Gly	missense	Exon 8 of 11	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 5169 AN: 108796 Hom.: 253 Cov.: 20

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

GnomAD2 exomes AF: 0.0318 AC: 5812 AN: 182935 AF XY: 0.0255

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 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

African (AFR) AF: 0.149 AC: 3926 AN: 26386

American (AMR) AF: 0.0862 AC: 3033 AN: 35192

Ashkenazi Jewish (ASJ) AF: 0.00480 AC: 93 AN: 19374

East Asian (EAS) AF: 0.0325 AC: 980 AN: 30200

South Asian (SAS) AF: 0.0270 AC: 1463 AN: 54128

European-Finnish (FIN) AF: 0.00323 AC: 130 AN: 40304

Middle Eastern (MID) AF: 0.0160 AC: 66 AN: 4133

European-Non Finnish (NFE) AF: 0.00547 AC: 4604 AN: 841577

Other (OTH) AF: 0.0203 AC: 935 AN: 46074

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

African (AFR) AF: 0.137 AC: 4071 AN: 29741

American (AMR) AF: 0.0486 AC: 496 AN: 10203

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 6 AN: 2613

East Asian (EAS) AF: 0.0265 AC: 91 AN: 3430

South Asian (SAS) AF: 0.0281 AC: 70 AN: 2488

European-Finnish (FIN) AF: 0.00384 AC: 22 AN: 5736

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.00641 AC: 335 AN: 52281

Other (OTH) AF: 0.0410 AC: 60 AN: 1465

Alfa AF: 0.0493 Hom.: 857

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 v4.9

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
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.3
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.13
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.028	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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

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