rs193139

Positions:

• chr1-108941353-T-C

Variant summary

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

The NM_001377458.1(CLCC1):​c.796+52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,465,260 control chromosomes in the GnomAD database, including 18,657 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 0.19 (3580 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15077 hom.)
• Consequence: CLCC1 NM_001377458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

Genes affected

CLCC1 (HGNC:29675): (chloride channel CLIC like 1) Predicted to enable chloride channel activity. Predicted to be involved in chloride transport. Located in endoplasmic reticulum and mitochondria-associated endoplasmic reticulum membrane. Implicated in retinitis pigmentosa 32. [provided by Alliance of Genome Resources, Apr 2022]

AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCC1	NM_001377458.1	c.796+52A>G		intron_variant		ENST00000369969.7	NP_001364387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCC1	ENST00000369969.7	c.796+52A>G		intron_variant		5	NM_001377458.1	ENSP00000358986	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29504 AN: 152086 Hom.: 3569 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.144 AC: 189247 AN: 1313056 Hom.: 15077 Cov.: 17 AF XY: 0.144 AC XY: 95258 AN XY: 660514

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.0164

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.194 AC: 29563 AN: 152204 Hom.: 3580 Cov.: 32 AF XY: 0.191 AC XY: 14225 AN XY: 74432

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.172

Alfa AF: 0.157 Hom.: 2699

Bravo AF: 0.200

Asia WGS AF: 0.0980 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs193139; hg19: chr1-109483975; COSMIC: COSV56763542;