6-31157072-C-T

Variant names:

• chr6-31157072-C-T
• rs3130453
• NM_001105564.2:c.234G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001105564.2(CCHCR1):​c.234G>A​(p.Trp78*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,608,130 control chromosomes in the GnomAD database, including 187,598 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.48 (17722 hom., cov: 32)
  • Exomes 𝑓: 0.48 (169876 hom.)
• Consequence: CCHCR1 NM_001105564.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 70 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 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.234G>A	p.Trp78*	stop_gained	Exon 2 of 18	NP_001099034.1
	CCHCR1	NM_001394641.1		c.261G>A	p.Trp87*	stop_gained	Exon 2 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.234G>A	p.Trp78*	stop_gained	Exon 2 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.234G>A	p.Trp78*	stop_gained	Exon 2 of 18	ENSP00000379566.3
	CCHCR1	ENST00000451521.6	TSL:1	c.234G>A	p.Trp78*	stop_gained	Exon 2 of 18	ENSP00000401039.2
	CCHCR1	ENST00000509552.5	TSL:1	n.108G>A		non_coding_transcript_exon	Exon 2 of 14

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73061 AN: 151904 Hom.: 17717 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.469

GnomAD2 exomes AF: 0.468 AC: 114039 AN: 243836 AF XY: 0.468

Gnomad AFR exome AF: 0.492

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.597

Gnomad EAS exome AF: 0.377

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.481 AC: 700088 AN: 1456108 Hom.: 169876 Cov.: 34 AF XY: 0.480 AC XY: 348003 AN XY: 724352

African (AFR) AF: 0.499 AC: 16665 AN: 33408

American (AMR) AF: 0.481 AC: 21429 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 15559 AN: 26048

East Asian (EAS) AF: 0.371 AC: 14708 AN: 39696

South Asian (SAS) AF: 0.471 AC: 40495 AN: 86006

European-Finnish (FIN) AF: 0.403 AC: 20956 AN: 52038

Middle Eastern (MID) AF: 0.523 AC: 3009 AN: 5754

European-Non Finnish (NFE) AF: 0.485 AC: 538065 AN: 1108434

Other (OTH) AF: 0.485 AC: 29202 AN: 60186

GnomAD4 genome AF: 0.481 AC: 73091 AN: 152022 Hom.: 17722 Cov.: 32 AF XY: 0.477 AC XY: 35411 AN XY: 74310

African (AFR) AF: 0.495 AC: 20498 AN: 41436

American (AMR) AF: 0.511 AC: 7811 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2038 AN: 5176

South Asian (SAS) AF: 0.458 AC: 2213 AN: 4828

European-Finnish (FIN) AF: 0.401 AC: 4235 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32596 AN: 67960

Other (OTH) AF: 0.469 AC: 993 AN: 2116

Alfa AF: 0.484 Hom.: 82658

Bravo AF: 0.490

TwinsUK AF: 0.496 AC: 1840

ALSPAC AF: 0.482 AC: 1857

ESP6500AA AF: 0.491 AC: 1483

ESP6500EA AF: 0.482 AC: 2610

ExAC AF: 0.465 AC: 54539

Asia WGS AF: 0.451 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.34	N
PhyloP100		0.27
Vest4		0.86
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=168/32	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3130453; hg19: chr6-31124849; COSMIC: COSV66161753; COSMIC: COSV66161753;