rs1265074

Positions:

• chr6-31145437-C-A

Variant summary

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

The NM_001105564.2(CCHCR1):​c.1739+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,692 control chromosomes in the GnomAD database, including 35,959 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 0.21 (3496 hom., cov: 33)
  • Exomes 𝑓: 0.21 (32463 hom.)
• Consequence: CCHCR1 NM_001105564.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.848

Genes affected

CCHCR1 (HGNC:13930): (coiled-coil alpha-helical rod protein 1) This gene encodes a protein with five coiled-coil alpha-helical rod domains that is thought to act as a regulator of mRNA metabolism through its interaction with mRNA-decapping protein 4. It localizes to P-bodies, the site of mRNA metabolism, with an N-terminus that is required for this subcellular localization, suggesting it is a P-body component. Naturally occurring mutations in this gene are associated with psoriasis. [provided by RefSeq, May 2017]

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 (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCHCR1	NM_001105564.2	c.1739+11G>T		intron_variant		ENST00000396268.8	NP_001099034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8	c.1739+11G>T		intron_variant		1	NM_001105564.2	ENSP00000379566	A2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31951 AN: 151978 Hom.: 3495 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.228 AC: 57373 AN: 251426 Hom.: 7080 AF XY: 0.225 AC XY: 30559 AN XY: 135882

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.0982

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.241

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.206 AC: 300787 AN: 1461596 Hom.: 32463 Cov.: 44 AF XY: 0.206 AC XY: 149482 AN XY: 727114

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.210 AC: 31966 AN: 152096 Hom.: 3496 Cov.: 33 AF XY: 0.214 AC XY: 15913 AN XY: 74360

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.192

Alfa AF: 0.193 Hom.: 3206

Bravo AF: 0.214

Asia WGS AF: 0.312 AC: 1083 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	19
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1265074; hg19: chr6-31113214; COSMIC: COSV66185689; COSMIC: COSV66185689;