rs130065

Variant names:

• chr6-31154723-G-A
• rs130065
• NM_001105564.2:c.574C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001105564.2(CCHCR1):​c.574C>T​(p.Arg192Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,608,406 control chromosomes in the GnomAD database, including 36,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2208 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33882 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.50
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002022177).
• BP6: Variant 6-31154723-G-A is Benign according to our data. Variant chr6-31154723-G-A is described in ClinVar as Benign. ClinVar VariationId is 1242555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2	c.574C>T	p.Arg192Trp	missense_variant	Exon 4 of 18	ENST00000396268.8	NP_001099034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8	c.574C>T	p.Arg192Trp	missense_variant	Exon 4 of 18	1	NM_001105564.2	ENSP00000379566.3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24639 AN: 152072 Hom.: 2205 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.0968

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.149 AC: 35749 AN: 240280 AF XY: 0.152

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.0693

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.0313

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.206 AC: 299897 AN: 1456216 Hom.: 33882 Cov.: 40 AF XY: 0.203 AC XY: 147349 AN XY: 724744

African (AFR) AF: 0.115 AC: 3836 AN: 33476

American (AMR) AF: 0.0729 AC: 3258 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4781 AN: 26122

East Asian (EAS) AF: 0.0218 AC: 865 AN: 39700

South Asian (SAS) AF: 0.121 AC: 10471 AN: 86240

European-Finnish (FIN) AF: 0.136 AC: 6528 AN: 48062

Middle Eastern (MID) AF: 0.163 AC: 942 AN: 5768

European-Non Finnish (NFE) AF: 0.231 AC: 257304 AN: 1111810

Other (OTH) AF: 0.197 AC: 11912 AN: 60336

GnomAD4 genome AF: 0.162 AC: 24646 AN: 152190 Hom.: 2208 Cov.: 32 AF XY: 0.156 AC XY: 11600 AN XY: 74402

African (AFR) AF: 0.123 AC: 5117 AN: 41524

American (AMR) AF: 0.0964 AC: 1474 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3470

East Asian (EAS) AF: 0.0399 AC: 207 AN: 5186

South Asian (SAS) AF: 0.108 AC: 523 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1446 AN: 10600

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14627 AN: 67982

Other (OTH) AF: 0.143 AC: 301 AN: 2112

Alfa AF: 0.196 Hom.: 8078

Bravo AF: 0.158

TwinsUK AF: 0.239 AC: 885

ALSPAC AF: 0.239 AC: 923

ESP6500AA AF: 0.136 AC: 410

ESP6500EA AF: 0.205 AC: 1110

ExAC AF: 0.149 AC: 17518

Asia WGS AF: 0.0700 AC: 247 AN: 3478

EpiCase AF: 0.212

EpiControl AF: 0.200

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	.;T;T;.;T;T;T;.;T;T;T;.;T;.;.
Eigen	Benign	0.023
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.84	.;.;.;T;T;T;.;T;T;T;.;T;.;.;T
MetaRNN	Benign	0.0020	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.;.;.;.;.;.;.;.;.;.;.;.;.
PhyloP100		1.5
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.080
Sift	Benign	0.039	D;D;D;D;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Uncertain	0.037	D;D;D;D;.;.;.;.;.;T;.;.;.;.;.
Polyphen		0.066	B;B;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.36
MPC		0.51
ClinPred		0.050	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.094
gMVP		0.35
Mutation Taster		=97/3	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: rs130065; hg19: chr6-31122500; COSMIC: COSV66161108; COSMIC: COSV66161108;