chr1-108941353-T-C

Variant names:

• chr1-108941353-T-C
• rs193139
• NM_001377458.1:c.796+52A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377458.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCC1	NM_001377458.1	MANE Select	c.796+52A>G		intron	N/A	NP_001364387.1
	CLCC1	NM_001048210.3		c.796+52A>G		intron	N/A	NP_001041675.1
	CLCC1	NM_001377459.1		c.796+52A>G		intron	N/A	NP_001364388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCC1	ENST00000369969.7	TSL:5 MANE Select	c.796+52A>G		intron	N/A	ENSP00000358986.3
	CLCC1	ENST00000302500.5	TSL:1	c.433+52A>G		intron	N/A	ENSP00000306552.4
	CLCC1	ENST00000348264.6	TSL:1	c.340-1571A>G		intron	N/A	ENSP00000337243.2

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

African (AFR) AF: 0.333 AC: 10004 AN: 30000

American (AMR) AF: 0.159 AC: 6462 AN: 40720

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5055 AN: 24540

East Asian (EAS) AF: 0.0164 AC: 633 AN: 38670

South Asian (SAS) AF: 0.141 AC: 11372 AN: 80576

European-Finnish (FIN) AF: 0.154 AC: 8112 AN: 52760

Middle Eastern (MID) AF: 0.204 AC: 1101 AN: 5388

European-Non Finnish (NFE) AF: 0.140 AC: 137956 AN: 985118

Other (OTH) AF: 0.155 AC: 8552 AN: 55284

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

African (AFR) AF: 0.329 AC: 13657 AN: 41480

American (AMR) AF: 0.149 AC: 2278 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3472

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5182

South Asian (SAS) AF: 0.124 AC: 601 AN: 4832

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10616

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10067 AN: 68008

Other (OTH) AF: 0.172 AC: 364 AN: 2114

Alfa AF: 0.162 Hom.: 3675

Bravo AF: 0.200

Asia WGS AF: 0.0980 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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