6-31144707-C-T

Variant names:

• chr6-31144707-C-T
• rs130072
• NM_001105564.2:c.2147G>A

Variant summary

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

The NM_001105564.2(CCHCR1):​c.2147G>A​(p.Arg716Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,610,764 control chromosomes in the GnomAD database, including 6,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.085 (662 hom., cov: 31)
  • Exomes 𝑓: 0.079 (5404 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 46 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=0.0021642745).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 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.2147G>A	p.Arg716Gln	missense	Exon 15 of 18	NP_001099034.1
	CCHCR1	NM_001394641.1		c.2174G>A	p.Arg725Gln	missense	Exon 15 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.2039G>A	p.Arg680Gln	missense	Exon 15 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.2147G>A	p.Arg716Gln	missense	Exon 15 of 18	ENSP00000379566.3
	CCHCR1	ENST00000451521.6	TSL:1	c.2039G>A	p.Arg680Gln	missense	Exon 15 of 18	ENSP00000401039.2
	CCHCR1	ENST00000376266.9	TSL:1	c.1880G>A	p.Arg627Gln	missense	Exon 15 of 18	ENSP00000365442.5

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12884 AN: 152080 Hom.: 662 Cov.: 31

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.0942

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.102 AC: 25424 AN: 250152 AF XY: 0.102

Gnomad AFR exome AF: 0.0515

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.0452

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.0865

Gnomad OTH exome AF: 0.0949

GnomAD4 exome AF: 0.0794 AC: 115815 AN: 1458566 Hom.: 5404 Cov.: 31 AF XY: 0.0804 AC XY: 58290 AN XY: 725136

African (AFR) AF: 0.0499 AC: 1670 AN: 33444

American (AMR) AF: 0.156 AC: 6961 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3567 AN: 26012

East Asian (EAS) AF: 0.0460 AC: 1824 AN: 39616

South Asian (SAS) AF: 0.0991 AC: 8516 AN: 85966

European-Finnish (FIN) AF: 0.163 AC: 8677 AN: 53276

Middle Eastern (MID) AF: 0.115 AC: 665 AN: 5758

European-Non Finnish (NFE) AF: 0.0711 AC: 78883 AN: 1109626

Other (OTH) AF: 0.0838 AC: 5052 AN: 60284

GnomAD4 genome AF: 0.0847 AC: 12894 AN: 152198 Hom.: 662 Cov.: 31 AF XY: 0.0891 AC XY: 6634 AN XY: 74416

African (AFR) AF: 0.0499 AC: 2070 AN: 41518

American (AMR) AF: 0.117 AC: 1790 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.0427 AC: 221 AN: 5174

South Asian (SAS) AF: 0.0942 AC: 455 AN: 4828

European-Finnish (FIN) AF: 0.180 AC: 1902 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0817 AC: 5558 AN: 68006

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.0845 Hom.: 2554

Bravo AF: 0.0804

TwinsUK AF: 0.0623 AC: 231

ALSPAC AF: 0.0667 AC: 257

ESP6500AA AF: 0.0531 AC: 234

ESP6500EA AF: 0.0867 AC: 746

ExAC AF: 0.0974 AC: 11819

Asia WGS AF: 0.0780 AC: 272 AN: 3478

EpiCase AF: 0.0959

EpiControl AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.083
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.25
MPC		0.83
ClinPred		0.012	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.43
Mutation Taster		=98/2	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: rs130072; hg19: chr6-31112484; COSMIC: COSV52550155; COSMIC: COSV52550155;