chr4-48998833-A-G

Variant names:

• chr4-48998833-A-G
• rs6850199
• NM_025087.3:c.802+285A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025087.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWH43	NM_025087.3	MANE Select	c.802+285A>G		intron	N/A	NP_079363.2	Q9H720
	CWH43	NM_001286791.2		c.721+285A>G		intron	N/A	NP_001273720.1	E7EQL2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWH43	ENST00000226432.9	TSL:1 MANE Select	c.802+285A>G		intron	N/A	ENSP00000226432.4	Q9H720
	CWH43	ENST00000856986.1		c.802+285A>G		intron	N/A	ENSP00000527045.1
	CWH43	ENST00000856987.1		c.802+285A>G		intron	N/A	ENSP00000527046.1

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

African (AFR) AF: 0.264 AC: 10951 AN: 41468

American (AMR) AF: 0.752 AC: 11470 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2609 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1942 AN: 5166

South Asian (SAS) AF: 0.516 AC: 2478 AN: 4806

European-Finnish (FIN) AF: 0.730 AC: 7708 AN: 10566

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49517 AN: 67972

Other (OTH) AF: 0.648 AC: 1367 AN: 2108

Alfa AF: 0.632 Hom.: 21389

Bravo AF: 0.577

Asia WGS AF: 0.463 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.40
PhyloP100		-0.24
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: rs6850199; hg19: chr4-49000850;