rs2791498

Variant names:

• chr1-86491941-G-T
• rs2791498
• NM_001285.4:c.1464+570G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001285.4(CLCA1):​c.1464+570G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 150,810 control chromosomes in the GnomAD database, including 13,526 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 0.41 (13526 hom., cov: 33)
• Consequence: CLCA1 NM_001285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798
• Publications: 3 publications found

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]

LOC124904210 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001285.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCA1	NM_001285.4	MANE Select	c.1464+570G>T		intron	N/A	NP_001276.3	A8K7I4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCA1	ENST00000394711.2	TSL:1 MANE Select	c.1464+570G>T		intron	N/A	ENSP00000378200.1	A8K7I4
	CLCA1	ENST00000234701.7	TSL:1	c.1464+570G>T		intron	N/A	ENSP00000234701.3	A8K7I4
	CLCA1	ENST00000957889.1		c.1461+570G>T		intron	N/A	ENSP00000627948.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62519 AN: 150692 Hom.: 13524 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.415 AC: 62544 AN: 150810 Hom.: 13526 Cov.: 33 AF XY: 0.411 AC XY: 30284 AN XY: 73596

African (AFR) AF: 0.305 AC: 12460 AN: 40918

American (AMR) AF: 0.463 AC: 6995 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1540 AN: 3462

East Asian (EAS) AF: 0.174 AC: 880 AN: 5062

South Asian (SAS) AF: 0.396 AC: 1851 AN: 4676

European-Finnish (FIN) AF: 0.430 AC: 4488 AN: 10428

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32755 AN: 67864

Other (OTH) AF: 0.420 AC: 882 AN: 2098

Alfa AF: 0.432 Hom.: 2450

Bravo AF: 0.408

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.58
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2791498; hg19: chr1-86957624;