2-202952595-C-A

Variant names:

• chr2-202952595-C-A
• NM_024744.17:c.343C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024744.17(CARF):​c.343C>A​(p.Leu115Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CARF NM_024744.17 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

Genes affected

CARF (HGNC:14435): (calcium responsive transcription factor) Enables DNA binding activity and DNA-binding transcription factor activity. Involved in cellular response to potassium ion and positive regulation of transcription from RNA polymerase II promoter in response to calcium ion. Predicted to be located in granular component. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

WDR12 (HGNC:14098): (WD repeat domain 12) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein is highly similar to the mouse WD repeat domain 12 protein at the amino acid level. The protein encoded by this gene is a component of a nucleolar protein complex that affects maturation of the large ribosomal subunit.[provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23008311).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024744.17. 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
	CARF	NM_024744.17	MANE Select	c.343C>A	p.Leu115Ile	missense	Exon 6 of 17	NP_079020.13
	CARF	NM_001104586.4		c.343C>A	p.Leu115Ile	missense	Exon 5 of 16	NP_001098056.1	Q8N187-1
	CARF	NM_001322427.3		c.343C>A	p.Leu115Ile	missense	Exon 6 of 17	NP_001309356.1	Q8N187-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARF	ENST00000438828.4	TSL:1 MANE Select	c.343C>A	p.Leu115Ile	missense	Exon 6 of 17	ENSP00000414644.1	Q8N187-1
	CARF	ENST00000402905.7	TSL:1	c.343C>A	p.Leu115Ile	missense	Exon 5 of 16	ENSP00000384006.2	Q8N187-1
	CARF	ENST00000444724.5	TSL:1	c.343C>A	p.Leu115Ile	missense	Exon 5 of 8	ENSP00000416812.1	F6SXV3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461614 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727120

African (AFR) AF: 0.00 AC: 0 AN: 33474

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111844

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.12
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.094
Sift	Uncertain	0.023	D
Sift4G	Benign	0.093	T
Polyphen		0.99	D
Vest4		0.43
MutPred		0.25		Gain of sheet (P = 0.0221)
MVP		0.34
MPC		0.77
ClinPred		0.90	D
GERP RS		3.6
Varity_R		0.075
gMVP		0.24
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

hg19: chr2-203817318;