rs11725957

Positions:

• chr4-49060875-G-A
• chr4-49060875-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_025087.3(CWH43):​c.2022-937G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 152,126 control chromosomes in the GnomAD database, including 33 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 0.019 (33 hom., cov: 32)
• Consequence: CWH43 NM_025087.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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 (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2826/152126) while in subpopulation NFE AF= 0.0285 (1937/67972). AF 95% confidence interval is 0.0274. There are 33 homozygotes in gnomad4. There are 1299 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWH43	NM_025087.3	c.2022-937G>A		intron_variant		ENST00000226432.9	NP_079363.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWH43	ENST00000226432.9	c.2022-937G>A		intron_variant		1	NM_025087.3	ENSP00000226432.4
CWH43	ENST00000513409.1	c.1941-937G>A		intron_variant		2		ENSP00000422802.1
CWH43	ENST00000514053.6	n.*1032-937G>A		intron_variant		5		ENSP00000425157.2

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2827 AN: 152008 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00563

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00727

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0186 AC: 2826 AN: 152126 Hom.: 33 Cov.: 32 AF XY: 0.0175 AC XY: 1299 AN XY: 74382

Gnomad4 AFR AF: 0.00561

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00728

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0260 Hom.: 65

Bravo AF: 0.0181

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.62

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: rs11725957; hg19: chr4-49062892;