6-31143103-C-T

Variant names:

• chr6-31143103-C-T
• rs1313140045
• NM_001105564.2:c.2351G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001105564.2(CCHCR1):​c.2351G>A​(p.Arg784His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07618421).
• BP6: Variant 6-31143103-C-T is Benign according to our data. Variant chr6-31143103-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3139673.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2351G>A	p.Arg784His	missense	Exon 17 of 18	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.2378G>A	p.Arg793His	missense	Exon 17 of 18	NP_001381570.1
	CCHCR1	NM_001105563.3		c.2243G>A	p.Arg748His	missense	Exon 17 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.2351G>A	p.Arg784His	missense	Exon 17 of 18	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.2243G>A	p.Arg748His	missense	Exon 17 of 18	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.2084G>A	p.Arg695His	missense	Exon 17 of 18	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460748 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726690

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74252

African (AFR) AF: 0.0000966 AC: 4 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.49	N
PhyloP100		-1.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.065
Sift	Benign	0.036	D
Sift4G	Benign	0.18	T
Polyphen		0.0070	B
Vest4		0.093
MutPred		0.60		Loss of MoRF binding (P = 0.0162)
MVP		0.076
MPC		0.53
ClinPred		0.081	T
GERP RS		-7.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.032
gMVP		0.12
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1313140045; hg19: chr6-31110880;