dbSNP rs2791519: CLCA1:c.-261+35T>G (chr1-86468493-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000234701.7(CLCA1):c.-261+35T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,072 control chromosomes in the GnomAD database, including 28,696 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 0.61 ( 28668 hom., cov: 31)

Exomes 𝑓: 0.63 ( 28 hom. )

Consequence

CLCA1
ENST00000234701.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.804

Publications

6 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCA1	ENST00000234701.7 link	c.-261+35T>G		intron_variant	Intron 1 of 14	1		ENSP00000234701.3		A8K7I4

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

93031

AN:

151812

Hom.:

28661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.657

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.622

GnomAD4 exome

AF:

0.634

AC:

AN:

142

Hom.:

Cov.:

AF XY:

0.681

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.625

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.583

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.612

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.613

AC:

93060

AN:

151930

Hom.:

28668

Cov.:

AF XY:

0.610

AC XY:

45266

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.569

AC:

23559

AN:

41420

American (AMR)

AF:

0.663

AC:

10124

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

2279

AN:

3470

East Asian (EAS)

AF:

0.524

AC:

2701

AN:

5154

South Asian (SAS)

AF:

0.505

AC:

2431

AN:

4814

European-Finnish (FIN)

AF:

0.612

AC:

6438

AN:

10526

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.641

AC:

43542

AN:

67962

Other (OTH)

AF:

0.616

AC:

1299

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1836

3672

5507

7343

9179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.634

Hom.:

39471

Bravo

AF:

0.616

Asia WGS

AF:

0.495

AC:

1722

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.20

(source)

DANN

Benign

0.49

PhyloP100

-0.80

PromoterAI

-0.014

Neutral

(source)

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over