rs1051447

chr4-49061855-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.58 (28780 hom., cov: 32)
  • Exomes 𝑓: 0.66 (275786 hom.)
• Consequence: CWH43 NM_025087.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07

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]

ACMG classification

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/exons	MANE	UniProt
CWH43	NM_025087.3	c.2065C>A	p.His689Asn	missense_variant	16/16	ENST00000226432.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWH43	ENST00000226432.9	c.2065C>A	p.His689Asn	missense_variant	16/16	1	NM_025087.3	P1
CWH43	ENST00000513409.1	c.1984C>A	p.His662Asn	missense_variant	16/16	2
CWH43	ENST00000514053.6	c.*1075C>A		3_prime_UTR_variant, NMD_transcript_variant	14/14	5

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88083 AN: 151770 Hom.: 28775 Cov.: 32

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

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.: 27 AF XY: 0.663 AC XY: 394448 AN XY: 595210

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.: 32 AF XY: 0.582 AC XY: 43191 AN XY: 74248

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	T
BayesDel_noAF	Benign	-0.52
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0072	T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.50	T;T
MetaRNN	Benign	0.0000016	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	0.084	P;P
PrimateAI	Uncertain	0.51	T
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	T
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

Other links and lift over

dbSNP: rs1051447; hg19: chr4-49063872; COSMIC: COSV56936745;