chrX-153935586-C-A

Variant names:

• chrX-153935586-C-A
• rs183725640
• NM_002910.6:c.1078-10G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002910.6(RENBP):​c.1078-10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,196,309 control chromosomes in the GnomAD database, including 17 homozygotes. There are 362 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., 36 hem., cov: 25)
  • Exomes 𝑓: 0.0011 (16 hom. 326 hem.)
• Consequence: RENBP NM_002910.6 intron
• Scores: Splicing: ADA: 0.0001877
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.222
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant X-153935586-C-A is Benign according to our data. Variant chrX-153935586-C-A is described in ClinVar as Benign. ClinVar VariationId is 785000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00114 (1238/1083305) while in subpopulation AMR AF = 0.0238 (836/35142). AF 95% confidence interval is 0.0225. There are 16 homozygotes in GnomAdExome4. There are 326 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 36 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.1078-10G>T		intron	N/A	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.1078-10G>T		intron	N/A	ENSP00000377303.3	P51606-1
	RENBP	ENST00000875215.1		c.1204-10G>T		intron	N/A	ENSP00000545274.1
	RENBP	ENST00000369997.7	TSL:5	c.1036-10G>T		intron	N/A	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 143 AN: 112951 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.0000642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000358

Gnomad FIN AF: 0.000319

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000451

Gnomad OTH AF: 0.00198

GnomAD2 exomes AF: 0.00435 AC: 779 AN: 178971 AF XY: 0.00275

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0257

Gnomad ASJ exome AF: 0.000272

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000375

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00114 AC: 1238 AN: 1083305 Hom.: 16 Cov.: 28 AF XY: 0.000932 AC XY: 326 AN XY: 349735

African (AFR) AF: 0.0000766 AC: 2 AN: 26114

American (AMR) AF: 0.0238 AC: 836 AN: 35142

Ashkenazi Jewish (ASJ) AF: 0.000415 AC: 8 AN: 19261

East Asian (EAS) AF: 0.00 AC: 0 AN: 30124

South Asian (SAS) AF: 0.000558 AC: 30 AN: 53748

European-Finnish (FIN) AF: 0.000379 AC: 15 AN: 39596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 0.000366 AC: 304 AN: 829798

Other (OTH) AF: 0.000943 AC: 43 AN: 45616

GnomAD4 genome AF: 0.00127 AC: 143 AN: 113004 Hom.: 1 Cov.: 25 AF XY: 0.00102 AC XY: 36 AN XY: 35156

African (AFR) AF: 0.0000640 AC: 2 AN: 31238

American (AMR) AF: 0.0103 AC: 111 AN: 10775

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.000359 AC: 1 AN: 2785

European-Finnish (FIN) AF: 0.000319 AC: 2 AN: 6267

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000451 AC: 24 AN: 53264

Other (OTH) AF: 0.00196 AC: 3 AN: 1533

Alfa AF: 0.00138 Hom.: 9

Bravo AF: 0.00230

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.030
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: rs183725640; hg19: chrX-153201039;