rs2791519

chr1-86468493-T-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCA1	ENST00000234701.7	c.-261+35T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93031 AN: 151812 Hom.: 28661 Cov.: 31

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: 90 AN: 142 Hom.: 28 Cov.: 0 AF XY: 0.681 AC XY: 49 AN XY: 72

Gnomad4 AFR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.613 AC: 93060 AN: 151930 Hom.: 28668 Cov.: 31 AF XY: 0.610 AC XY: 45266 AN XY: 74252

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.616

Alfa AF: 0.636 Hom.: 30479

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
Dann	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs2791519; hg19: chr1-86934176;