rs772602

Variant names:

• chr1-86566247-C-T
• rs772602
• NM_012128.4:c.954+227C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012128.4(CLCA4):​c.954+227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,764 control chromosomes in the GnomAD database, including 23,964 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 0.55 (23964 hom., cov: 31)
• Consequence: CLCA4 NM_012128.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCA4	NM_012128.4	c.954+227C>T		intron_variant	Intron 6 of 13	ENST00000370563.3	NP_036260.2
CLCA4	NR_024602.2	n.887+227C>T		intron_variant	Intron 5 of 12
CLCA4	XM_011541015.3	c.801+227C>T		intron_variant	Intron 6 of 13		XP_011539317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCA4	ENST00000370563.3	c.954+227C>T		intron_variant	Intron 6 of 13	1	NM_012128.4	ENSP00000359594.3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82837 AN: 151648 Hom.: 23944 Cov.: 31

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.546 AC: 82886 AN: 151764 Hom.: 23964 Cov.: 31 AF XY: 0.554 AC XY: 41088 AN XY: 74164

African (AFR) AF: 0.347 AC: 14363 AN: 41394

American (AMR) AF: 0.661 AC: 10082 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2132 AN: 3464

East Asian (EAS) AF: 0.722 AC: 3716 AN: 5146

South Asian (SAS) AF: 0.699 AC: 3369 AN: 4818

European-Finnish (FIN) AF: 0.624 AC: 6572 AN: 10538

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40666 AN: 67850

Other (OTH) AF: 0.540 AC: 1137 AN: 2106

Alfa AF: 0.591 Hom.: 12621

Bravo AF: 0.542

Asia WGS AF: 0.657 AC: 2284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.9
DANN	Benign	0.67
PhyloP100		-0.18
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: rs772602; hg19: chr1-87031930; COSMIC: COSV55367213; COSMIC: COSV55367213;