rs130076

Positions:

• chr6-31154705-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001105564.2(CCHCR1):​c.592C>T​(p.Arg198Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,609,422 control chromosomes in the GnomAD database, including 37,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2434 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35034 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011596978).
• BP6: Variant 6-31154705-G-A is Benign according to our data. Variant chr6-31154705-G-A is described in ClinVar as [Benign]. Clinvar id is 1283507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCHCR1	NM_001105564.2	c.592C>T	p.Arg198Trp	missense_variant	4/18	ENST00000396268.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCHCR1	ENST00000396268.8	c.592C>T	p.Arg198Trp	missense_variant	4/18	1	NM_001105564.2	A2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25992 AN: 152100 Hom.: 2430 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.156 AC: 37608 AN: 241488 Hom.: 3542 AF XY: 0.160 AC XY: 21115 AN XY: 132160

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0751

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.0318

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.210 AC: 306354 AN: 1457204 Hom.: 35034 Cov.: 41 AF XY: 0.208 AC XY: 150869 AN XY: 725186

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0793

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.171 AC: 26001 AN: 152218 Hom.: 2434 Cov.: 32 AF XY: 0.165 AC XY: 12284 AN XY: 74432

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.153

Alfa AF: 0.203 Hom.: 3410

Bravo AF: 0.168

TwinsUK AF: 0.240 AC: 891

ALSPAC AF: 0.241 AC: 930

ESP6500AA AF: 0.157 AC: 474

ESP6500EA AF: 0.210 AC: 1138

ExAC AF: 0.157 AC: 18338

Asia WGS AF: 0.0750 AC: 264 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.208

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 22182809) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.16	N
MetaRNN	Benign	0.0012	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.064
Sift	Benign	0.064	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Uncertain	0.053	T;T;T;D;.;.;.;.;.;T;.;.;.;.;.
Polyphen		0.017	B;B;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.20
MPC		0.51
ClinPred		0.035	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.25

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: rs130076; hg19: chr6-31122482; COSMIC: COSV66161104; COSMIC: COSV66161104;