6-31154538-G-C

Variant names:

• chr6-31154538-G-C
• rs130066
• NM_001105564.2:c.759C>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.759C>G​(p.Ser253Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,612,068 control chromosomes in the GnomAD database, including 150,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.41 (12542 hom., cov: 33)
  • Exomes 𝑓: 0.43 (138215 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 47 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=0.0037828386).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001105564.2	c.759C>G	p.Ser253Arg	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.759C>G	p.Ser253Arg	missense_variant	Exon 4 of 18	1	NM_001105564.2	ENSP00000379566.3

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61597 AN: 151974 Hom.: 12538 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.383

GnomAD2 exomes AF: 0.405 AC: 99566 AN: 245652 AF XY: 0.404

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.428

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.366

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.432 AC: 631436 AN: 1459976 Hom.: 138215 Cov.: 44 AF XY: 0.430 AC XY: 312002 AN XY: 726270

African (AFR) AF: 0.365 AC: 12203 AN: 33472

American (AMR) AF: 0.429 AC: 19192 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 10579 AN: 26126

East Asian (EAS) AF: 0.362 AC: 14350 AN: 39684

South Asian (SAS) AF: 0.381 AC: 32886 AN: 86234

European-Finnish (FIN) AF: 0.368 AC: 19220 AN: 52294

Middle Eastern (MID) AF: 0.417 AC: 2406 AN: 5764

European-Non Finnish (NFE) AF: 0.445 AC: 495052 AN: 1111332

Other (OTH) AF: 0.423 AC: 25548 AN: 60354

GnomAD4 genome AF: 0.405 AC: 61617 AN: 152092 Hom.: 12542 Cov.: 33 AF XY: 0.402 AC XY: 29860 AN XY: 74328

African (AFR) AF: 0.371 AC: 15392 AN: 41484

American (AMR) AF: 0.433 AC: 6616 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1361 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1973 AN: 5170

South Asian (SAS) AF: 0.369 AC: 1783 AN: 4832

European-Finnish (FIN) AF: 0.362 AC: 3824 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29323 AN: 67972

Other (OTH) AF: 0.383 AC: 808 AN: 2112

Alfa AF: 0.413 Hom.: 4387

Bravo AF: 0.411

TwinsUK AF: 0.460 AC: 1707

ALSPAC AF: 0.456 AC: 1757

ESP6500AA AF: 0.377 AC: 1140

ESP6500EA AF: 0.429 AC: 2323

ExAC AF: 0.404 AC: 47434

Asia WGS AF: 0.392 AC: 1361 AN: 3478

EpiCase AF: 0.418

EpiControl AF: 0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.0094	.;T;T;.;T;T;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.67	.;.;.;T;T;T;.;T
MetaRNN	Benign	0.0038	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	.;M;.;.;.;.;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	0.080	N;N;N;N;N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.66	T;T;T;T;T;T;T;T
Sift4G	Benign	0.44	T;T;T;T;.;.;.;.
Polyphen		0.0040	B;B;.;.;.;.;.;.
Vest4		0.35
MutPred		0.16		.;Loss of phosphorylation at S164 (P = 0.0084);Loss of phosphorylation at S164 (P = 0.0084);.;.;.;Loss of phosphorylation at S164 (P = 0.0084);.;
MPC		0.50
ClinPred		0.0053	T
GERP RS		3.5
Varity_R		0.038
gMVP		0.45
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs130066; hg19: chr6-31122315; COSMIC: COSV66161360; COSMIC: COSV66161360;