X-153942913-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002910.6(RENBP):c.629C>T(p.Ala210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,209,051 control chromosomes in the GnomAD database, including 60 homozygotes. There are 888 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (33 hom., 424 hem., cov: 24)
  • Exomes 𝑓: 0.0016 (27 hom. 464 hem.)
• Consequence: RENBP NM_002910.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.35

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00233683).
• BP6: Variant X-153942913-G-A is Benign according to our data. Variant chrX-153942913-G-A is described in ClinVar as [Benign]. Clinvar id is 786400.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (1650/112015) while in subpopulation AFR AF= 0.0505 (1558/30839). AF 95% confidence interval is 0.0484. There are 33 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RENBP	NM_002910.6	c.629C>T	p.Ala210Val	missense_variant	6/11	ENST00000393700.8
RENBP	XM_017029698.2	c.599C>T	p.Ala200Val	missense_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RENBP	ENST00000393700.8	c.629C>T	p.Ala210Val	missense_variant	6/11	1	NM_002910.6	P1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 1648 AN: 111968 Hom.: 33 Cov.: 24 AF XY: 0.0124 AC XY: 426 AN XY: 34238

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00560

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00468 AC: 853 AN: 182167 Hom.: 14 AF XY: 0.00324 AC XY: 218 AN XY: 67273

Gnomad AFR exome AF: 0.0559

Gnomad AMR exome AF: 0.00329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000524

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00155 AC: 1704 AN: 1097036 Hom.: 27 Cov.: 32 AF XY: 0.00128 AC XY: 464 AN XY: 362772

Gnomad4 AFR exome AF: 0.0490

Gnomad4 AMR exome AF: 0.00330

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000663

Gnomad4 SAS exome AF: 0.0000924

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000150

Gnomad4 OTH exome AF: 0.00337

GnomAD4 genome AF: 0.0147 AC: 1650 AN: 112015 Hom.: 33 Cov.: 24 AF XY: 0.0124 AC XY: 424 AN XY: 34295

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.00559

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000163

Gnomad4 NFE AF: 0.000226

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00187 Hom.: 12

Bravo AF: 0.0178

ESP6500AA AF: 0.0553 AC: 212

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00494 AC: 600

EpiCase AF: 0.000109

EpiControl AF: 0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.95
Cadd	Benign	14
Dann	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.64	T;T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.079
Sift	Benign	0.42	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.33	B;.
Vest4		0.097
MVP		0.32
MPC		0.41
ClinPred		0.0078	T
GERP RS		2.1
Varity_R		0.072
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs142718878; hg19: chrX-153208365;