1-86566247-C-T

Position:

• chr1-86566247-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
CLCA4	NM_012128.4	c.954+227C>T		intron_variant		ENST00000370563.3	NP_036260.2
CLCA4	XM_011541015.3	c.801+227C>T		intron_variant			XP_011539317.1
CLCA4	NR_024602.2	n.887+227C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCA4	ENST00000370563.3	c.954+227C>T		intron_variant		1	NM_012128.4	ENSP00000359594	P1

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

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.540

Alfa AF: 0.595 Hom.: 10735

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

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: rs772602; hg19: chr1-87031930; COSMIC: COSV55367213; COSMIC: COSV55367213;