Genetic Variant RGN:p.His142His (chrX-47089855-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_152869.4(RGN):c.426C>T(p.His142His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,205,454 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 43 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 0.000083 ( 0 hom., 1 hem., cov: 20)

Exomes 𝑓: 0.00010 ( 0 hom. 42 hem. )

Consequence

RGN
NM_152869.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.63

Publications

0 publications found

Variant links:

Genes affected

RGN (HGNC:9989): (regucalcin) The protein encoded by this gene is a highly conserved, calcium-binding protein, that is preferentially expressed in the liver and kidney. It may have an important role in calcium homeostasis. Studies in rat indicate that this protein may also play a role in aging, as it shows age-associated down-regulation. This gene is part of a gene cluster on chromosome Xp11.3-Xp11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

RGN links:

ENSG00000307069 (HGNC:):

ENSG00000307069 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-1.63 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 42 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152869.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGN	NM_152869.4	MANE Select	c.426C>T	p.His142His	synonymous	Exon 5 of 8	NP_690608.1	Q15493-1
RGN	NM_004683.6		c.426C>T	p.His142His	synonymous	Exon 4 of 7	NP_004674.1	Q15493-1
RGN	NM_001282848.2		c.267C>T	p.His89His	synonymous	Exon 5 of 8	NP_001269777.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGN	ENST00000397180.6	TSL:5 MANE Select	c.426C>T	p.His142His	synonymous	Exon 5 of 8	ENSP00000380365.1	Q15493-1
RGN	ENST00000336169.3	TSL:1	c.426C>T	p.His142His	synonymous	Exon 4 of 7	ENSP00000338400.3	Q15493-1
RGN	ENST00000352078.8	TSL:1	c.426C>T	p.His142His	synonymous	Exon 4 of 7	ENSP00000253303.4	Q15493-1

Frequencies

GnomAD3 genomes

AF:

0.0000828

AC:

AN:

108642

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000114

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000821

AC:

AN:

182688

AF XY:

0.000104

show subpopulations

Gnomad AFR exome

AF:

0.0000762

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

112

AN:

1096812

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

362214

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26376

American (AMR)

AF:

0.0000284

AC:

AN:

35185

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19360

East Asian (EAS)

AF:

0.00

AC:

AN:

30184

South Asian (SAS)

AF:

0.00

AC:

AN:

54067

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40483

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.000128

AC:

108

AN:

840986

Other (OTH)

AF:

0.0000434

AC:

AN:

46039

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000828

AC:

AN:

108642

Hom.:

Cov.:

AF XY:

0.0000322

AC XY:

AN XY:

31010

show subpopulations

African (AFR)

AF:

0.000101

AC:

AN:

29808

American (AMR)

AF:

0.00

AC:

AN:

9748

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2628

East Asian (EAS)

AF:

0.00

AC:

AN:

3474

South Asian (SAS)

AF:

0.00

AC:

AN:

2566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.000114

AC:

AN:

52629

Other (OTH)

AF:

0.00

AC:

AN:

1441

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.014

(source)

DANN

Benign

0.81

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

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

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