4-48998833-A-G

Position:

• chr4-48998833-A-G

Variant summary

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

The NM_025087.3(CWH43):​c.802+285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,020 control chromosomes in the GnomAD database, including 29,465 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 0.59 (29465 hom., cov: 31)
• Consequence: CWH43 NM_025087.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CWH43	NM_025087.3	c.802+285A>G		intron_variant		ENST00000226432.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CWH43	ENST00000226432.9	c.802+285A>G		intron_variant		1	NM_025087.3	P1
CWH43	ENST00000513409.1	c.721+285A>G		intron_variant		2
CWH43	ENST00000514053.6	c.*4009A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88909 AN: 151902 Hom.: 29459 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.585 AC: 88942 AN: 152020 Hom.: 29465 Cov.: 31 AF XY: 0.586 AC XY: 43503 AN XY: 74290

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.648

Alfa AF: 0.684 Hom.: 18367

Bravo AF: 0.577

Asia WGS AF: 0.463 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.40

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: rs6850199; hg19: chr4-49000850;