rs130076

Variant names:

• chr6-31154705-G-A
• rs130076
• NM_001105564.2:c.592C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31154705-G-A
• chr6-31154705-G-C
• chr6-31154705-G-T

Variant summary

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

The NM_001394649.1(CCHCR1):​c.-33C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,609,422 control chromosomes in the GnomAD database, including 37,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2434 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35034 hom.)
• Consequence: CCHCR1 NM_001394649.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17
• Publications: 57 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=0.0011596978).
• BP6: Variant 6-31154705-G-A is Benign according to our data. Variant chr6-31154705-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394649.1. 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.592C>T	p.Arg198Trp	missense	Exon 4 of 18	NP_001099034.1
	CCHCR1	NM_001394649.1		c.-33C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 16	NP_001381578.1
	CCHCR1	NM_001394641.1		c.619C>T	p.Arg207Trp	missense	Exon 4 of 18	NP_001381570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.592C>T	p.Arg198Trp	missense	Exon 4 of 18	ENSP00000379566.3
	CCHCR1	ENST00000451521.6	TSL:1	c.484C>T	p.Arg162Trp	missense	Exon 4 of 18	ENSP00000401039.2
	CCHCR1	ENST00000376266.9	TSL:1	c.325C>T	p.Arg109Trp	missense	Exon 4 of 18	ENSP00000365442.5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25992 AN: 152100 Hom.: 2430 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.156 AC: 37608 AN: 241488 AF XY: 0.160

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0751

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.0318

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.210 AC: 306354 AN: 1457204 Hom.: 35034 Cov.: 41 AF XY: 0.208 AC XY: 150869 AN XY: 725186

African (AFR) AF: 0.137 AC: 4575 AN: 33478

American (AMR) AF: 0.0793 AC: 3544 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 5025 AN: 26126

East Asian (EAS) AF: 0.0220 AC: 873 AN: 39698

South Asian (SAS) AF: 0.136 AC: 11702 AN: 86254

European-Finnish (FIN) AF: 0.136 AC: 6661 AN: 48964

Middle Eastern (MID) AF: 0.187 AC: 1077 AN: 5766

European-Non Finnish (NFE) AF: 0.234 AC: 260619 AN: 1111854

Other (OTH) AF: 0.203 AC: 12278 AN: 60356

GnomAD4 genome AF: 0.171 AC: 26001 AN: 152218 Hom.: 2434 Cov.: 32 AF XY: 0.165 AC XY: 12284 AN XY: 74432

African (AFR) AF: 0.142 AC: 5907 AN: 41538

American (AMR) AF: 0.106 AC: 1628 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3472

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5186

South Asian (SAS) AF: 0.123 AC: 594 AN: 4830

European-Finnish (FIN) AF: 0.136 AC: 1443 AN: 10604

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14913 AN: 67972

Other (OTH) AF: 0.153 AC: 323 AN: 2116

Alfa AF: 0.198 Hom.: 10859

Bravo AF: 0.168

TwinsUK AF: 0.240 AC: 891

ALSPAC AF: 0.241 AC: 930

ESP6500AA AF: 0.157 AC: 474

ESP6500EA AF: 0.210 AC: 1138

ExAC AF: 0.157 AC: 18338

Asia WGS AF: 0.0750 AC: 264 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.208

ClinVar

ClinVar submissions as Germline

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	0.095
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.2
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.064
Sift	Benign	0.064	T
Sift4G	Uncertain	0.053	T
Polyphen		0.017	B
Vest4		0.20
MPC		0.51
ClinPred		0.035	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.25
Mutation Taster		=96/4	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: rs130076; hg19: chr6-31122482; COSMIC: COSV66161104; COSMIC: COSV66161104;