rs1543467

Positions:

• chr1-86548977-G-A
• chr1-86548977-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370563.3(CLCA4):​c.159+1699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,014 control chromosomes in the GnomAD database, including 21,379 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 0.48 (21379 hom., cov: 32)
• Consequence: CLCA4 ENST00000370563.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCA4	NM_012128.4	c.159+1699G>A		intron_variant		ENST00000370563.3	NP_036260.2
CLCA4	NR_024602.2	n.201+1699G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCA4	ENST00000370563.3	c.159+1699G>A		intron_variant		1	NM_012128.4	ENSP00000359594	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72288 AN: 151896 Hom.: 21326 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.476 AC: 72392 AN: 152014 Hom.: 21379 Cov.: 32 AF XY: 0.477 AC XY: 35431 AN XY: 74332

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.452

Alfa AF: 0.359 Hom.: 4947

Bravo AF: 0.491

Asia WGS AF: 0.633 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs1543467; hg19: chr1-87014660;