1-86560247-A-C

Variant names:

• chr1-86560247-A-C
• NM_012128.4:c.337A>C
• CLCA4 p.Arg113Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012128.4(CLCA4):​c.337A>C​(p.Arg113Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R113R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLCA4 NM_012128.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

CLCA4 (HGNC:2018): (chloride channel accessory 4) The protein encoded by this gene belongs to the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same site on chromosome 1p31-p22 and share high degrees of homology in size, sequence and predicted structure, but differ significantly in their tissue distributions. Alternative splicing results in multiple transcript variants, only one of which is thought to be protein coding. [provided by RefSeq, Dec 2008]

CLCA4 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012128.4. 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
	CLCA4	NM_012128.4	MANE Select	c.337A>C	p.Arg113Arg	synonymous	Exon 3 of 14	NP_036260.2	Q14CN2-1
	CLCA4	NR_024602.2		n.379A>C		non_coding_transcript_exon	Exon 3 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCA4	ENST00000370563.3	TSL:1 MANE Select	c.337A>C	p.Arg113Arg	synonymous	Exon 3 of 14	ENSP00000359594.3	Q14CN2-1
	CLCA4	ENST00000862142.1		c.337A>C	p.Arg113Arg	synonymous	Exon 3 of 14	ENSP00000532201.1
	CLCA4	ENST00000862141.1		c.337A>C	p.Arg113Arg	synonymous	Exon 3 of 14	ENSP00000532200.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		1.7
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-87025930;