rs130068

Variant names:

• chr6-31148469-G-A
• rs130068
• NM_001105564.2:c.1516C>T

Variant summary

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

The NM_001105564.2(CCHCR1):​c.1516C>T​(p.Arg506Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,611,098 control chromosomes in the GnomAD database, including 160,187 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 0.44 (14675 hom., cov: 32)
  • Exomes 𝑓: 0.44 (145512 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 32 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=1.5869737E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	NM_001105564.2	MANE Select	c.1516C>T	p.Arg506Trp	missense	Exon 10 of 18	NP_001099034.1
	CCHCR1	NM_001394641.1		c.1543C>T	p.Arg515Trp	missense	Exon 10 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.1408C>T	p.Arg470Trp	missense	Exon 10 of 18	NP_001099033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.1516C>T	p.Arg506Trp	missense	Exon 10 of 18	ENSP00000379566.3
	CCHCR1	ENST00000451521.6	TSL:1	c.1408C>T	p.Arg470Trp	missense	Exon 10 of 18	ENSP00000401039.2
	CCHCR1	ENST00000376266.9	TSL:1	c.1249C>T	p.Arg417Trp	missense	Exon 10 of 18	ENSP00000365442.5

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66673 AN: 151924 Hom.: 14676 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.467

GnomAD2 exomes AF: 0.440 AC: 108347 AN: 246312 AF XY: 0.445

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.407

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.296

Gnomad FIN exome AF: 0.512

Gnomad NFE exome AF: 0.448

Gnomad OTH exome AF: 0.460

GnomAD4 exome AF: 0.443 AC: 647025 AN: 1459056 Hom.: 145512 Cov.: 41 AF XY: 0.445 AC XY: 323115 AN XY: 725864

African (AFR) AF: 0.419 AC: 14031 AN: 33452

American (AMR) AF: 0.413 AC: 18472 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 13915 AN: 26120

East Asian (EAS) AF: 0.289 AC: 11481 AN: 39694

South Asian (SAS) AF: 0.458 AC: 39447 AN: 86182

European-Finnish (FIN) AF: 0.514 AC: 26877 AN: 52308

Middle Eastern (MID) AF: 0.543 AC: 3128 AN: 5762

European-Non Finnish (NFE) AF: 0.443 AC: 491865 AN: 1110508

Other (OTH) AF: 0.461 AC: 27809 AN: 60324

GnomAD4 genome AF: 0.439 AC: 66695 AN: 152042 Hom.: 14675 Cov.: 32 AF XY: 0.440 AC XY: 32713 AN XY: 74316

African (AFR) AF: 0.422 AC: 17479 AN: 41462

American (AMR) AF: 0.408 AC: 6224 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1501 AN: 5150

South Asian (SAS) AF: 0.420 AC: 2022 AN: 4820

European-Finnish (FIN) AF: 0.527 AC: 5582 AN: 10588

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30421 AN: 67964

Other (OTH) AF: 0.464 AC: 981 AN: 2112

Alfa AF: 0.448 Hom.: 33848

Bravo AF: 0.434

TwinsUK AF: 0.436 AC: 1617

ALSPAC AF: 0.434 AC: 1674

ESP6500AA AF: 0.434 AC: 1312

ESP6500EA AF: 0.444 AC: 2408

ExAC AF: 0.437 AC: 51479

Asia WGS AF: 0.421 AC: 1468 AN: 3478

EpiCase AF: 0.473

EpiControl AF: 0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.00016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.21
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.021
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.0030	B
Vest4		0.15
MPC		0.46
ClinPred		0.0053	T
GERP RS		1.1
Varity_R		0.12
gMVP		0.19
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: rs130068; hg19: chr6-31116246; COSMIC: COSV66183532; COSMIC: COSV66183532;