chr6-31144960-C-A

Variant names:

• chr6-31144960-C-A
• rs130079
• NM_001105564.2:c.1990G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001105564.2(CCHCR1):​c.1990G>T​(p.Gly664Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,610,436 control chromosomes in the GnomAD database, including 43,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3111 hom., cov: 31)
  • Exomes 𝑓: 0.23 (40437 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76
• Publications: 42 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022124648).
• BP6: Variant 6-31144960-C-A is Benign according to our data. Variant chr6-31144960-C-A is described in ClinVar as Benign. ClinVar VariationId is 1291637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 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.1990G>T	p.Gly664Cys	missense	Exon 14 of 18	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.2017G>T	p.Gly673Cys	missense	Exon 14 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.1882G>T	p.Gly628Cys	missense	Exon 14 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.1990G>T	p.Gly664Cys	missense	Exon 14 of 18	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.1882G>T	p.Gly628Cys	missense	Exon 14 of 18	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.1723G>T	p.Gly575Cys	missense	Exon 14 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29820 AN: 151982 Hom.: 3108 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.194

GnomAD2 exomes AF: 0.177 AC: 44097 AN: 248736 AF XY: 0.179

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.0318

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.227 AC: 331057 AN: 1458336 Hom.: 40437 Cov.: 36 AF XY: 0.224 AC XY: 162788 AN XY: 725632

African (AFR) AF: 0.178 AC: 5966 AN: 33470

American (AMR) AF: 0.120 AC: 5387 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 7901 AN: 26124

East Asian (EAS) AF: 0.0222 AC: 880 AN: 39700

South Asian (SAS) AF: 0.138 AC: 11884 AN: 86244

European-Finnish (FIN) AF: 0.139 AC: 6940 AN: 50088

Middle Eastern (MID) AF: 0.219 AC: 1264 AN: 5768

European-Non Finnish (NFE) AF: 0.249 AC: 276963 AN: 1111854

Other (OTH) AF: 0.230 AC: 13872 AN: 60368

GnomAD4 genome AF: 0.196 AC: 29827 AN: 152100 Hom.: 3111 Cov.: 31 AF XY: 0.189 AC XY: 14027 AN XY: 74350

African (AFR) AF: 0.180 AC: 7483 AN: 41474

American (AMR) AF: 0.148 AC: 2257 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3468

East Asian (EAS) AF: 0.0410 AC: 212 AN: 5174

South Asian (SAS) AF: 0.125 AC: 600 AN: 4812

European-Finnish (FIN) AF: 0.137 AC: 1457 AN: 10598

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16042 AN: 67978

Other (OTH) AF: 0.191 AC: 402 AN: 2106

Alfa AF: 0.220 Hom.: 10787

Bravo AF: 0.198

TwinsUK AF: 0.256 AC: 948

ALSPAC AF: 0.258 AC: 995

ESP6500AA AF: 0.190 AC: 835

ESP6500EA AF: 0.236 AC: 2031

ExAC AF: 0.178 AC: 21582

Asia WGS AF: 0.0800 AC: 279 AN: 3478

EpiCase AF: 0.240

EpiControl AF: 0.228

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.040
Sift	Benign	0.14	T
Sift4G	Benign	0.090	T
Polyphen		0.099	B
Vest4		0.31
MPC		0.59
ClinPred		0.014	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.16
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: rs130079; hg19: chr6-31112737; COSMIC: COSV52546238; COSMIC: COSV52546238;