X-153942092-A-G

Variant names:

• chrX-153942092-A-G
• rs2269372
• NM_002910.6:c.688-61T>C

Variant summary

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

The NM_002910.6(RENBP):​c.688-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 930,495 control chromosomes in the GnomAD database, including 36,362 homozygotes. There are 80,029 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 0.38 (8090 hom., 11956 hem., cov: 21)
  • Exomes 𝑓: 0.27 (28272 hom. 68073 hem.)
• Consequence: RENBP NM_002910.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 14 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RENBP	NM_002910.6	MANE Select	c.688-61T>C		intron	N/A	NP_002901.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RENBP	ENST00000393700.8	TSL:1 MANE Select	c.688-61T>C		intron	N/A	ENSP00000377303.3
	RENBP	ENST00000369997.7	TSL:5	c.646-61T>C		intron	N/A	ENSP00000359014.3
	RENBP	ENST00000423624.5	TSL:5	n.*509-61T>C		intron	N/A	ENSP00000394220.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 41744 AN: 108865 Hom.: 8081 Cov.: 21

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.0696

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.267 AC: 219605 AN: 821587 Hom.: 28272 Cov.: 13 AF XY: 0.319 AC XY: 68073 AN XY: 213529

African (AFR) AF: 0.708 AC: 15317 AN: 21642

American (AMR) AF: 0.617 AC: 20737 AN: 33596

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 4997 AN: 16888

East Asian (EAS) AF: 0.755 AC: 21726 AN: 28781

South Asian (SAS) AF: 0.585 AC: 27727 AN: 47407

European-Finnish (FIN) AF: 0.180 AC: 7079 AN: 39300

Middle Eastern (MID) AF: 0.423 AC: 1519 AN: 3592

European-Non Finnish (NFE) AF: 0.183 AC: 108536 AN: 593295

Other (OTH) AF: 0.323 AC: 11967 AN: 37086

GnomAD4 genome AF: 0.384 AC: 41795 AN: 108908 Hom.: 8090 Cov.: 21 AF XY: 0.382 AC XY: 11956 AN XY: 31290

African (AFR) AF: 0.693 AC: 20622 AN: 29778

American (AMR) AF: 0.502 AC: 5171 AN: 10296

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 676 AN: 2615

East Asian (EAS) AF: 0.765 AC: 2618 AN: 3423

South Asian (SAS) AF: 0.601 AC: 1494 AN: 2486

European-Finnish (FIN) AF: 0.173 AC: 988 AN: 5726

Middle Eastern (MID) AF: 0.380 AC: 79 AN: 208

European-Non Finnish (NFE) AF: 0.181 AC: 9477 AN: 52218

Other (OTH) AF: 0.420 AC: 623 AN: 1483

Alfa AF: 0.354 Hom.: 6402

Bravo AF: 0.426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.87
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2269372; hg19: chrX-153207545; COSMIC: COSV64169783; COSMIC: COSV64169783;