6-31142614-G-C

Variant names:

• chr6-31142614-G-C
• rs1576
• NM_001105564.2:c.2594C>G

Variant summary

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

The NM_001105564.2(CCHCR1):​c.2594C>G​(p.Ser865Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,611,658 control chromosomes in the GnomAD database, including 77,250 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 0.28 (6262 hom., cov: 33)
  • Exomes 𝑓: 0.31 (70988 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 62 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=0.0013647377).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 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.2594C>G	p.Ser865Cys	missense	Exon 18 of 18	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.2621C>G	p.Ser874Cys	missense	Exon 18 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.2486C>G	p.Ser829Cys	missense	Exon 18 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.2594C>G	p.Ser865Cys	missense	Exon 18 of 18	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.2486C>G	p.Ser829Cys	missense	Exon 18 of 18	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.2327C>G	p.Ser776Cys	missense	Exon 18 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42989 AN: 152080 Hom.: 6262 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.0834

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.308

GnomAD2 exomes AF: 0.278 AC: 69694 AN: 250546 AF XY: 0.280

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.0769

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.310

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.306 AC: 446964 AN: 1459460 Hom.: 70988 Cov.: 34 AF XY: 0.305 AC XY: 221086 AN XY: 725938

African (AFR) AF: 0.233 AC: 7774 AN: 33436

American (AMR) AF: 0.277 AC: 12367 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11482 AN: 26116

East Asian (EAS) AF: 0.0681 AC: 2702 AN: 39688

South Asian (SAS) AF: 0.237 AC: 20417 AN: 86206

European-Finnish (FIN) AF: 0.299 AC: 15725 AN: 52622

Middle Eastern (MID) AF: 0.333 AC: 1894 AN: 5680

European-Non Finnish (NFE) AF: 0.320 AC: 355675 AN: 1110706

Other (OTH) AF: 0.314 AC: 18928 AN: 60304

GnomAD4 genome AF: 0.283 AC: 43008 AN: 152198 Hom.: 6262 Cov.: 33 AF XY: 0.279 AC XY: 20792 AN XY: 74400

African (AFR) AF: 0.236 AC: 9800 AN: 41534

American (AMR) AF: 0.265 AC: 4062 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1446 AN: 3472

East Asian (EAS) AF: 0.0836 AC: 433 AN: 5182

South Asian (SAS) AF: 0.219 AC: 1060 AN: 4830

European-Finnish (FIN) AF: 0.317 AC: 3355 AN: 10586

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21613 AN: 67972

Other (OTH) AF: 0.305 AC: 645 AN: 2114

Alfa AF: 0.317 Hom.: 1799

Bravo AF: 0.281

TwinsUK AF: 0.318 AC: 1180

ALSPAC AF: 0.325 AC: 1254

ESP6500AA AF: 0.248 AC: 1094

ESP6500EA AF: 0.323 AC: 2776

ExAC AF: 0.275 AC: 33442

Asia WGS AF: 0.158 AC: 551 AN: 3478

EpiCase AF: 0.336

EpiControl AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.3
DANN	Benign	0.67
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.28	N
PhyloP100		-0.47
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.016
Sift	Benign	0.14	T
Sift4G	Benign	0.093	T
Polyphen		0.0	B
Vest4		0.079
MPC		0.41
ClinPred		0.0038	T
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.15
Mutation Taster		=100/0	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: rs1576; hg19: chr6-31110391; COSMIC: COSV52535538; COSMIC: COSV52535538;