11-67365147-GAGCCCCC-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBS1BS2
The NM_013246.3(CLCF1):c.660_666delGGGGGCT(p.Gly221MetfsTer6) variant causes a frameshift change. The variant allele was found at a frequency of 0.00115 in 1,613,946 control chromosomes in the GnomAD database, including 23 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_013246.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLCF1 | NM_013246.3 | c.660_666delGGGGGCT | p.Gly221MetfsTer6 | frameshift_variant | Exon 3 of 3 | ENST00000312438.8 | NP_037378.1 | |
CLCF1 | NM_001166212.2 | c.630_636delGGGGGCT | p.Gly211MetfsTer6 | frameshift_variant | Exon 3 of 3 | NP_001159684.1 | ||
LOC100130987 | NR_024469.1 | n.424-22385_424-22379delCCCCCAG | intron_variant | Intron 2 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLCF1 | ENST00000312438.8 | c.660_666delGGGGGCT | p.Gly221MetfsTer6 | frameshift_variant | Exon 3 of 3 | 1 | NM_013246.3 | ENSP00000309338.7 | ||
ENSG00000256514 | ENST00000543494.1 | c.16+8370_16+8376delGGGGGCT | intron_variant | Intron 1 of 3 | 3 | ENSP00000480527.1 | ||||
CLCF1 | ENST00000533438.1 | c.630_636delGGGGGCT | p.Gly211MetfsTer6 | frameshift_variant | Exon 3 of 3 | 2 | ENSP00000434122.1 | |||
RAD9A | ENST00000622583.4 | n.392-22385_392-22379delCCCCCAG | intron_variant | Intron 2 of 3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00575 AC: 876AN: 152228Hom.: 14 Cov.: 32
GnomAD3 exomes AF: 0.00153 AC: 383AN: 250902Hom.: 7 AF XY: 0.00108 AC XY: 147AN XY: 135762
GnomAD4 exome AF: 0.000666 AC: 973AN: 1461600Hom.: 9 AF XY: 0.000620 AC XY: 451AN XY: 727084
GnomAD4 genome AF: 0.00575 AC: 876AN: 152346Hom.: 14 Cov.: 32 AF XY: 0.00558 AC XY: 416AN XY: 74496
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: CLCF1 c.660_666delGGGGGCT (p.Gly221MetfsX6) causes a frameshift which results in an extension of the protein. The variant allele was found at a frequency of 0.0015 in 250902 control chromosomes, predominantly at a frequency of 0.021 within the African or African-American subpopulation in the gnomAD database, including 7 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 84 fold of the estimated maximal expected allele frequency for a pathogenic variant in CLCF1 causing Cold-Induced Sweating Syndrome phenotype (0.00025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.660_666delGGGGGCT in individuals affected with Cold-Induced Sweating Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at