chr1-86557652-G-T

Variant names:

• chr1-86557652-G-T
• rs6684219
• NM_012128.4:c.160-2280G>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.160-2280G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,028 control chromosomes in the GnomAD database, including 24,014 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 (24014 hom., cov: 31)
• Consequence: CLCA4 NM_012128.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 1 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=-0.79).
• 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.160-2280G>T		intron_variant	Intron 1 of 13	ENST00000370563.3	NP_036260.2
CLCA4	NR_024602.2	n.202-2280G>T		intron_variant	Intron 1 of 12
CLCA4	XM_011541015.3	c.7-2280G>T		intron_variant	Intron 1 of 13		XP_011539317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCA4	ENST00000370563.3	c.160-2280G>T		intron_variant	Intron 1 of 13	1	NM_012128.4	ENSP00000359594.3

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83197 AN: 151910 Hom.: 23993 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.548 AC: 83248 AN: 152028 Hom.: 24014 Cov.: 31 AF XY: 0.555 AC XY: 41255 AN XY: 74310

African (AFR) AF: 0.348 AC: 14410 AN: 41446

American (AMR) AF: 0.661 AC: 10105 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3470

East Asian (EAS) AF: 0.723 AC: 3731 AN: 5162

South Asian (SAS) AF: 0.701 AC: 3382 AN: 4822

European-Finnish (FIN) AF: 0.625 AC: 6603 AN: 10564

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

European-Non Finnish (NFE) AF: 0.602 AC: 40884 AN: 67960

Other (OTH) AF: 0.540 AC: 1142 AN: 2114

Alfa AF: 0.568 Hom.: 3082

Bravo AF: 0.543

Asia WGS AF: 0.656 AC: 2280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.9
DANN	Benign	0.76
PhyloP100		-0.65
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: rs6684219; hg19: chr1-87023335;