Genetic Variant NM_002910.6:c.1078-10G>T (chrX-153935586-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.000932

AC XY:

326

AN XY:

349735

show subpopulations

African (AFR)

AF:

0.0000766

AC:

AN:

26114

American (AMR)

AF:

0.0238

AC:

836

AN:

35142

Ashkenazi Jewish (ASJ)

AF:

0.000415

AC:

AN:

19261

East Asian (EAS)

AF:

0.00

AC:

AN:

30124

South Asian (SAS)

AF:

0.000558

AC:

AN:

53748

European-Finnish (FIN)

AF:

0.000379

AC:

AN:

39596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3906

European-Non Finnish (NFE)

AF:

0.000366

AC:

304

AN:

829798

Other (OTH)

AF:

0.000943

AC:

AN:

45616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00127

AC:

143

AN:

113004

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

35156

show subpopulations

African (AFR)

AF:

0.0000640

AC:

AN:

31238

American (AMR)

AF:

0.0103

AC:

111

AN:

10775

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

3585

South Asian (SAS)

AF:

0.000359

AC:

AN:

2785

European-Finnish (FIN)

AF:

0.000319

AC:

AN:

6267

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000451

AC:

AN:

53264

Other (OTH)

AF:

0.00196

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.00138

Hom.:

Bravo

AF:

0.00230

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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