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. 15/21 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
• Publications: 122 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105564.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	NM_001105564.2	MANE Select	c.1092A>C	p.Glu364Asp	missense	Exon 6 of 18	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.1119A>C	p.Glu373Asp	missense	Exon 6 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.984A>C	p.Glu328Asp	missense	Exon 6 of 18	NP_001099033.1	Q8TD31-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.1092A>C	p.Glu364Asp	missense	Exon 6 of 18	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.984A>C	p.Glu328Asp	missense	Exon 6 of 18	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.825A>C	p.Glu275Asp	missense	Exon 6 of 18	ENSP00000365442.5	Q8TD31-1

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

African (AFR) AF: 0.190 AC: 6367 AN: 33460

American (AMR) AF: 0.309 AC: 13791 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2672 AN: 26078

East Asian (EAS) AF: 0.339 AC: 13472 AN: 39692

South Asian (SAS) AF: 0.243 AC: 20958 AN: 86164

European-Finnish (FIN) AF: 0.228 AC: 11944 AN: 52274

Middle Eastern (MID) AF: 0.199 AC: 1146 AN: 5768

European-Non Finnish (NFE) AF: 0.196 AC: 218249 AN: 1111364

Other (OTH) 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

African (AFR) AF: 0.195 AC: 8087 AN: 41500

American (AMR) AF: 0.286 AC: 4371 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3472

East Asian (EAS) AF: 0.340 AC: 1757 AN: 5166

South Asian (SAS) AF: 0.244 AC: 1177 AN: 4822

European-Finnish (FIN) AF: 0.224 AC: 2373 AN: 10602

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13264 AN: 68006

Other (OTH) AF: 0.192 AC: 406 AN: 2114

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 v4.9

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
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
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.38
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.016
Sift	Benign	0.63	T
Sift4G	Benign	0.24	T
Polyphen		0.0030	B
Vest4		0.087
MutPred		0.20		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

Other links and lift over

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