Genetic Variant CHPF:p.Arg730His (chr2-219539522-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024536.6(CHPF):c.2189G>A(p.Arg730His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,764 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

CHPF
NM_024536.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.283

Publications

4 publications found

Variant links:

Genes affected

CHPF (HGNC:24291): (chondroitin polymerizing factor) Enables N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity and glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity. Involved in chondroitin sulfate biosynthetic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHPF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013954401).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024536.6. 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
	CHPF	NM_024536.6	MANE Select	c.2189G>A	p.Arg730His	missense	Exon 4 of 4	NP_078812.3
	CHPF	NM_001195731.2		c.1703G>A	p.Arg568His	missense	Exon 4 of 4	NP_001182660.2	Q8IZ52-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHPF	ENST00000243776.11	TSL:1 MANE Select	c.2189G>A	p.Arg730His	missense	Exon 4 of 4	ENSP00000243776.6	Q8IZ52-1
CHPF	ENST00000691864.1		c.2165G>A	p.Arg722His	missense	Exon 4 of 4	ENSP00000509104.1	A0A8I5QJC8
CHPF	ENST00000919936.1		c.2111G>A	p.Arg704His	missense	Exon 4 of 4	ENSP00000589995.1

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000363

AC:

AN:

250428

AF XY:

0.000295

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000872

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000513

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000246

AC:

360

AN:

1461396

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33476

American (AMR)

AF:

0.000157

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26110

East Asian (EAS)

AF:

0.000882

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.0000564

AC:

AN:

53154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000249

AC:

277

AN:

1111880

Other (OTH)

AF:

0.000265

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000532

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.000841

AC:

AN:

41596

American (AMR)

AF:

0.000196

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000559

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0042

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PhyloP100

-0.28

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

REVEL

Benign

0.069

Sift

Benign

0.30

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.067

MVP

0.27

MPC

0.29

ClinPred

0.025

GERP RS

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.48

Mutation Taster

=84/16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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