Variant 1-86482267-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001285.4(CLCA1):c.620C>T(p.Thr207Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CLCA1
NM_001285.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.73

Variant links:

Genes affected

CLCA1 (HGNC:2015): (chloride channel accessory 1) This gene encodes a member of the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same region on chromosome 1p31-p22 and share a high degree of homology in size, sequence, and predicted structure, but differ significantly in their tissue distributions. The encoded protein is expressed as a precursor protein that is processed into two cell-surface-associated subunits, although the site at which the precursor is cleaved has not been precisely determined. The encoded protein may be involved in mediating calcium-activated chloride conductance in the intestine. [provided by RefSeq, Jul 2008]

CLCA1 links:

LOC124904210 (HGNC:):

LOC124904210 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0087412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCA1	NM_001285.4 linkuse as main transcript	c.620C>T	p.Thr207Ile	missense_variant	5/14	ENST00000394711.2
LOC124904210	XR_007066206.1 linkuse as main transcript	n.226-1459G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCA1	ENST00000394711.2 linkuse as main transcript	c.620C>T	p.Thr207Ile	missense_variant	5/14	1	NM_001285.4	P1
CLCA1	ENST00000234701.7 linkuse as main transcript	c.620C>T	p.Thr207Ile	missense_variant	6/15	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251338

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461560

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000309

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000272

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.620C>T (p.T207I) alteration is located in exon 5 (coding exon 5) of the CLCA1 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the threonine (T) at amino acid position 207 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0030

DANN

Benign

0.80

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.045

.;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.0087

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.014

Sift

Benign

0.20

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0010

B;B

Vest4

0.11

MVP

0.076

MPC

0.074

ClinPred

0.017

GERP RS

-5.0

Varity_R

0.048

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over