Genetic Variant RENBP:c.1166-4G>A (chrX-153935408-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002910.6(RENBP):c.1166-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,136,686 control chromosomes in the GnomAD database, including 78 homozygotes. There are 2,086 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 5 hom., 97 hem., cov: 24)

Exomes 𝑓: 0.0035 ( 73 hom. 1989 hem. )

Consequence

RENBP
NM_002910.6 splice_region, intron

Scores

Splicing: ADA: 0.00003076

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.764

Publications

0 publications found

Variant links:

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]

RENBP links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-153935408-C-T is Benign according to our data. Variant chrX-153935408-C-T is described in ClinVar as Benign. ClinVar VariationId is 723213.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.062 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.1166-4G>A		splice_region intron	N/A	NP_002901.2	P51606-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RENBP	ENST00000393700.8	TSL:1 MANE Select	c.1166-4G>A	splice_region intron	N/A	ENSP00000377303.3	P51606-1
RENBP	ENST00000875215.1		c.1292-4G>A	splice_region intron	N/A	ENSP00000545274.1
RENBP	ENST00000369997.7	TSL:5	c.1124-4G>A	splice_region intron	N/A	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

197

AN:

111872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.0710

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00693

AC:

917

AN:

132251

AF XY:

0.0109

show subpopulations

Gnomad AFR exome

AF:

0.0000996

Gnomad AMR exome

AF:

0.0000498

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000907

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000170

Gnomad OTH exome

AF:

0.00388

GnomAD4 exome

AF:

0.00350

AC:

3587

AN:

1024765

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

1989

AN XY:

312371

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

24287

American (AMR)

AF:

0.0000352

AC:

AN:

28424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16358

East Asian (EAS)

AF:

0.000139

AC:

AN:

28879

South Asian (SAS)

AF:

0.0709

AC:

3367

AN:

47507

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37480

Middle Eastern (MID)

AF:

0.00165

AC:

AN:

3638

European-Non Finnish (NFE)

AF:

0.0000415

AC:

AN:

795338

Other (OTH)

AF:

0.00404

AC:

173

AN:

42854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

142

214

285

356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00173

AC:

194

AN:

111921

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

AN XY:

34129

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30942

American (AMR)

AF:

0.00

AC:

AN:

10750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.000284

AC:

AN:

3515

South Asian (SAS)

AF:

0.0701

AC:

192

AN:

2738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52816

Other (OTH)

AF:

0.00

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000740

Hom.:

Bravo

AF:

0.000400

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

(source)

DANN

Benign

0.86

PhyloP100

-0.76

PromoterAI

0.054

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0020

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over