rs1517899

Positions:

• chr1-86638175-T-C
• chr1-86638175-T-G

Variant summary

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

The NR_024604.1(CLCA3P):​n.576-683T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,924 control chromosomes in the GnomAD database, including 12,615 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 0.40 (12615 hom., cov: 32)
• Consequence: CLCA3P NR_024604.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

Genes affected

CLCA3P (HGNC:2017): (chloride channel accessory 3, pseudogene) This gene is a transcribed pseudogene belonging 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. This gene contains several nonsense codons compared to other family members that render the transcript a candidate for nonsense-mediated mRNA decay (NMD). Therefore, this gene is unlikely to be protein-coding. [provided by RefSeq, Jan 2009]

CLCA4-AS1 (HGNC:54055): (CLCA4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCA3P	NR_024604.1	n.576-683T>C		intron_variant, non_coding_transcript_variant
CLCA4-AS1	NR_135837.1	n.1292+54988A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCA3P	ENST00000466454.1	n.576-683T>C		intron_variant, non_coding_transcript_variant		1
CLCA3P	ENST00000490028.5	n.576-683T>C		intron_variant, non_coding_transcript_variant
CLCA4-AS1	ENST00000699483.1	n.1283+54988A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61338 AN: 151804 Hom.: 12606 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.404 AC: 61389 AN: 151924 Hom.: 12615 Cov.: 32 AF XY: 0.393 AC XY: 29206 AN XY: 74228

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.422

Alfa AF: 0.313 Hom.: 1076

Bravo AF: 0.422

Asia WGS AF: 0.368 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1517899; hg19: chr1-87103858;