4-49027884-C-T

Variant names:

• chr4-49027884-C-T
• rs2768975
• NM_025087.3:c.1267-745C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025087.3(CWH43):​c.1267-745C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,868 control chromosomes in the GnomAD database, including 30,277 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.

• Frequency: Genomes: 𝑓 0.60 (30277 hom., cov: 30)
• Consequence: CWH43 NM_025087.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWH43	NM_025087.3	c.1267-745C>T		intron_variant	Intron 9 of 15	ENST00000226432.9	NP_079363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWH43	ENST00000226432.9	c.1267-745C>T		intron_variant	Intron 9 of 15	1	NM_025087.3	ENSP00000226432.4
CWH43	ENST00000513409.1	c.1186-745C>T		intron_variant	Intron 9 of 15	2		ENSP00000422802.1
CWH43	ENST00000514053.6	n.*277-745C>T		intron_variant	Intron 7 of 13	5		ENSP00000425157.2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91739 AN: 151752 Hom.: 30268 Cov.: 30

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.664

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.604 AC: 91788 AN: 151868 Hom.: 30277 Cov.: 30 AF XY: 0.605 AC XY: 44901 AN XY: 74226

African (AFR) AF: 0.331 AC: 13668 AN: 41348

American (AMR) AF: 0.767 AC: 11712 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2599 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1996 AN: 5154

South Asian (SAS) AF: 0.531 AC: 2553 AN: 4806

European-Finnish (FIN) AF: 0.732 AC: 7727 AN: 10554

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49214 AN: 67960

Other (OTH) AF: 0.663 AC: 1394 AN: 2102

Alfa AF: 0.632 Hom.: 18283

Bravo AF: 0.600

Asia WGS AF: 0.479 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.76
DANN	Benign	0.50
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2768975; hg19: chr4-49029901;