4-48988590-A-G

Variant names:

• chr4-48988590-A-G
• rs1322106360
• NM_025087.3:c.157A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_025087.3(CWH43):​c.157A>G​(p.Ile53Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CWH43 NM_025087.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.81
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05548784).
• BP6: Variant 4-48988590-A-G is Benign according to our data. Variant chr4-48988590-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3837570.Status of the report is criteria_provided_single_submitter, 1 stars.

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.157A>G	p.Ile53Val	missense	Exon 2 of 16	NP_079363.2	Q9H720
	CWH43	NM_001286791.2		c.76A>G	p.Ile26Val	missense	Exon 2 of 16	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.157A>G	p.Ile53Val	missense	Exon 2 of 16	ENSP00000226432.4	Q9H720
	CWH43	ENST00000856986.1		c.157A>G	p.Ile53Val	missense	Exon 2 of 16	ENSP00000527045.1
	CWH43	ENST00000856987.1		c.157A>G	p.Ile53Val	missense	Exon 2 of 16	ENSP00000527046.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461306 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111534

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0020
DANN	Benign	0.13
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		-2.8
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.018
Sift	Benign	0.55	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.33		Loss of glycosylation at S51 (P = 0.0635)
MVP		0.095
MPC		0.047
ClinPred		0.040	T
GERP RS		-10
Varity_R		0.020
gMVP		0.087
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1322106360; hg19: chr4-48990607;