chrX-153941620-C-T

Variant names:

• chrX-153941620-C-T
• rs781880066
• NM_002910.6:c.803G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002910.6(RENBP):​c.803G>A​(p.Arg268His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,197,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000050 (0 hom., 2 hem., cov: 19)
  • Exomes 𝑓: 0.000024 (0 hom. 7 hem.)
• Consequence: RENBP NM_002910.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.119
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09318456).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

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.803G>A	p.Arg268His	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.803G>A	p.Arg268His	missense	Exon 8 of 11	ENSP00000377303.3	P51606-1
	RENBP	ENST00000875215.1		c.803G>A	p.Arg268His	missense	Exon 8 of 12	ENSP00000545274.1
	RENBP	ENST00000369997.7	TSL:5	c.761G>A	p.Arg254His	missense	Exon 8 of 11	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes AF: 0.0000496 AC: 5 AN: 100906 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000746

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000348

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000222 AC: 4 AN: 180269 AF XY: 0.0000305

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000738

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000250

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000237 AC: 26 AN: 1096424 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 7 AN XY: 362194

African (AFR) AF: 0.0000379 AC: 1 AN: 26351

American (AMR) AF: 0.000114 AC: 4 AN: 35140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19350

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30064

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54005

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.0000214 AC: 18 AN: 841398

Other (OTH) AF: 0.00 AC: 0 AN: 46027

GnomAD4 genome AF: 0.0000496 AC: 5 AN: 100906 Hom.: 0 Cov.: 19 AF XY: 0.0000784 AC XY: 2 AN XY: 25506

African (AFR) AF: 0.0000746 AC: 2 AN: 26820

American (AMR) AF: 0.000348 AC: 3 AN: 8625

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2550

East Asian (EAS) AF: 0.00 AC: 0 AN: 3215

South Asian (SAS) AF: 0.00 AC: 0 AN: 2220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4669

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50614

Other (OTH) AF: 0.00 AC: 0 AN: 1323

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.12
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.080
Sift	Uncertain	0.023	D
Sift4G	Benign	0.32	T
Polyphen		0.99	D
Vest4		0.094
MVP		0.14
MPC		0.50
ClinPred		0.19	T
GERP RS		2.4
Varity_R		0.075
gMVP		0.28
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs781880066; hg19: chrX-153207073;