Genetic Variant CWH43:p.His689Asn (chr4-49061855-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025087.3(CWH43):c.2065C>A(p.His689Asn) variant causes a missense change. The variant allele was found at a frequency of 0.655 in 1,355,700 control chromosomes in the GnomAD database, including 304,566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.58 ( 28780 hom., cov: 32)

Exomes 𝑓: 0.66 ( 275786 hom. )

Consequence

CWH43
NM_025087.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.07

Variant links:

Genes affected

CWH43 (HGNC:26133): (cell wall biogenesis 43 C-terminal homolog) Predicted to be involved in GPI anchor biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

CWH43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6461898E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWH43	NM_025087.3 link	c.2065C>A	p.His689Asn	missense_variant	Exon 16 of 16	ENST00000226432.9	NP_079363.2	Q9H720

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CWH43	ENST00000226432.9 link	c.2065C>A	p.His689Asn	missense_variant	Exon 16 of 16	1	NM_025087.3	ENSP00000226432.4	Q9H720
CWH43	ENST00000513409.1 link	c.1984C>A	p.His662Asn	missense_variant	Exon 16 of 16	2		ENSP00000422802.1	E7EQL2
CWH43	ENST00000514053.6 link	n.*1075C>A		non_coding_transcript_exon_variant	Exon 14 of 14	5		ENSP00000425157.2	D6RDZ8
CWH43	ENST00000514053.6 link	n.*1075C>A		3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000425157.2	D6RDZ8

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88083

AN:

151770

Hom.:

28775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.744

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.743

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.731

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.645

GnomAD3 exomes

AF:

0.652

AC:

109027

AN:

167110

Hom.:

37687

AF XY:

0.659

AC XY:

61433

AN XY:

93212

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.792

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.354

Gnomad SAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.739

Gnomad NFE exome

AF:

0.718

Gnomad OTH exome

AF:

0.692

GnomAD4 exome

AF:

0.665

AC:

800303

AN:

1203812

Hom.:

275786

Cov.:

AF XY:

0.663

AC XY:

394448

AN XY:

595210

show subpopulations

Gnomad4 AFR exome

AF:

0.234

Gnomad4 AMR exome

AF:

0.763

Gnomad4 ASJ exome

AF:

0.717

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.531

Gnomad4 FIN exome

AF:

0.713

Gnomad4 NFE exome

AF:

0.692

Gnomad4 OTH exome

AF:

0.631

GnomAD4 genome

AF:

0.580

AC:

88114

AN:

151888

Hom.:

28780

Cov.:

AF XY:

0.582

AC XY:

43191

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.748

Gnomad4 ASJ

AF:

0.743

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.524

Gnomad4 FIN

AF:

0.731

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.642

Alfa

AF:

0.683

Hom.:

63714

Bravo

AF:

0.573

TwinsUK

AF:

0.697

AC:

2584

ALSPAC

AF:

0.702

AC:

2704

ESP6500AA

AF:

0.276

AC:

1204

ESP6500EA

AF:

0.713

AC:

6045

ExAC

AF:

0.648

AC:

78532

Asia WGS

AF:

0.460

AC:

1590

AN:

3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0000016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.082

Sift

Benign

0.37

T;T

Sift4G

Uncertain

0.019

D;D

Polyphen

0.96

D;.

Vest4

0.24

MPC

0.16

ClinPred

0.031

GERP RS

4.6

Varity_R

0.21

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over