rs130071

Positions:

• chr6-31148433-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001105564.2(CCHCR1):​c.1552C>T​(p.Leu518=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,608,940 control chromosomes in the GnomAD database, including 63,886 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 0.25 (4991 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58895 hom.)
• Consequence: CCHCR1 NM_001105564.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-0.233 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCHCR1	NM_001105564.2	c.1552C>T	p.Leu518=	synonymous_variant	10/18	ENST00000396268.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCHCR1	ENST00000396268.8	c.1552C>T	p.Leu518=	synonymous_variant	10/18	1	NM_001105564.2	A2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38269 AN: 151902 Hom.: 4991 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.0626

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.275

GnomAD3 exomes AF: 0.251 AC: 61811 AN: 245980 Hom.: 8433 AF XY: 0.253 AC XY: 33892 AN XY: 134070

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.387

Gnomad EAS exome AF: 0.0560

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.278 AC: 405645 AN: 1456920 Hom.: 58895 Cov.: 31 AF XY: 0.277 AC XY: 200576 AN XY: 724916

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.0553

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.252 AC: 38283 AN: 152020 Hom.: 4991 Cov.: 32 AF XY: 0.249 AC XY: 18475 AN XY: 74330

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.0627

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.273

Alfa AF: 0.280 Hom.: 8474

Bravo AF: 0.249

Asia WGS AF: 0.146 AC: 512 AN: 3478

EpiCase AF: 0.299

EpiControl AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.0
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs130071; hg19: chr6-31116210; COSMIC: COSV66183522; COSMIC: COSV66183522;