6-31150734-T-G

Variant names:

• chr6-31150734-T-G
• rs130067
• NM_001105564.2:c.1092A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105564.2(CCHCR1):​c.1092A>C​(p.Glu364Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,611,990 control chromosomes in the GnomAD database, including 35,893 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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 (3489 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32404 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005039245).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2	c.1092A>C	p.Glu364Asp	missense_variant	Exon 6 of 18	ENST00000396268.8	NP_001099034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8	c.1092A>C	p.Glu364Asp	missense_variant	Exon 6 of 18	1	NM_001105564.2	ENSP00000379566.3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31944 AN: 152050 Hom.: 3488 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.229 AC: 56419 AN: 246656 AF XY: 0.225

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.0983

Gnomad EAS exome AF: 0.335

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.206 AC: 300287 AN: 1459822 Hom.: 32404 Cov.: 36 AF XY: 0.205 AC XY: 149225 AN XY: 726240

Gnomad4 AFR exome AF: 0.190 AC: 6367 AN: 33460

Gnomad4 AMR exome AF: 0.309 AC: 13791 AN: 44670

Gnomad4 ASJ exome AF: 0.102 AC: 2672 AN: 26078

Gnomad4 EAS exome AF: 0.339 AC: 13472 AN: 39692

Gnomad4 SAS exome AF: 0.243 AC: 20958 AN: 86164

Gnomad4 FIN exome AF: 0.228 AC: 11944 AN: 52274

Gnomad4 NFE exome AF: 0.196 AC: 218249 AN: 1111364

Gnomad4 Remaining exome AF: 0.194 AC: 11688 AN: 60352

GnomAD4 genome AF: 0.210 AC: 31959 AN: 152168 Hom.: 3489 Cov.: 32 AF XY: 0.214 AC XY: 15898 AN XY: 74382

Gnomad4 AFR AF: 0.195 AC: 0.194867 AN: 0.194867

Gnomad4 AMR AF: 0.286 AC: 0.286023 AN: 0.286023

Gnomad4 ASJ AF: 0.107 AC: 0.107431 AN: 0.107431

Gnomad4 EAS AF: 0.340 AC: 0.340108 AN: 0.340108

Gnomad4 SAS AF: 0.244 AC: 0.24409 AN: 0.24409

Gnomad4 FIN AF: 0.224 AC: 0.223826 AN: 0.223826

Gnomad4 NFE AF: 0.195 AC: 0.195042 AN: 0.195042

Gnomad4 OTH AF: 0.192 AC: 0.192053 AN: 0.192053

Alfa AF: 0.200 Hom.: 13984

Bravo AF: 0.214

TwinsUK AF: 0.206 AC: 764

ALSPAC AF: 0.198 AC: 763

ESP6500AA AF: 0.192 AC: 580

ESP6500EA AF: 0.197 AC: 1069

ExAC AF: 0.227 AC: 26974

Asia WGS AF: 0.312 AC: 1083 AN: 3478

EpiCase AF: 0.178

EpiControl AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.8
DANN	Benign	0.97
DEOGEN2	Benign	0.0032	.;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.60	.;.;.;T
MetaRNN	Benign	0.0050	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	.;N;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.49	N;N;N;N
REVEL	Benign	0.016
Sift	Benign	0.63	T;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.0030	B;B;.;.
Vest4		0.087
MutPred		0.20		.;Loss of ubiquitination at K272 (P = 0.1264);Loss of ubiquitination at K272 (P = 0.1264);.;
MPC		0.39
ClinPred		0.0031	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.025
gMVP		0.058
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs130067; hg19: chr6-31118511; COSMIC: COSV66182542; COSMIC: COSV66182542;