6-31144825-G-C

Variant names:

• chr6-31144825-G-C
• rs1265078
• ENST00000509552.5:n.1999C>G

Variant summary

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

The ENST00000509552.5(CCHCR1):​n.1999C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,607,840 control chromosomes in the GnomAD database, including 76,992 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 0.28 (6184 hom., cov: 30)
  • Exomes 𝑓: 0.31 (70808 hom.)
• Consequence: CCHCR1 ENST00000509552.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 33 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509552.5. 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.2066-37C>G		intron	N/A	NP_001099034.1
	CCHCR1	NM_001394641.1		c.2093-37C>G		intron	N/A	NP_001381570.1
	CCHCR1	NM_001105563.3		c.1958-37C>G		intron	N/A	NP_001099033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000509552.5	TSL:1	n.1999C>G		non_coding_transcript_exon	Exon 14 of 14
	CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.2066-37C>G		intron	N/A	ENSP00000379566.3
	CCHCR1	ENST00000451521.6	TSL:1	c.1958-37C>G		intron	N/A	ENSP00000401039.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42642 AN: 151758 Hom.: 6185 Cov.: 30

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.0836

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.279 AC: 69989 AN: 251150 AF XY: 0.280

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.0771

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.306 AC: 446073 AN: 1455964 Hom.: 70808 Cov.: 30 AF XY: 0.305 AC XY: 220758 AN XY: 724412

African (AFR) AF: 0.228 AC: 7625 AN: 33398

American (AMR) AF: 0.277 AC: 12364 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11476 AN: 26092

East Asian (EAS) AF: 0.0681 AC: 2698 AN: 39628

South Asian (SAS) AF: 0.237 AC: 20409 AN: 86114

European-Finnish (FIN) AF: 0.302 AC: 16073 AN: 53292

Middle Eastern (MID) AF: 0.335 AC: 1929 AN: 5756

European-Non Finnish (NFE) AF: 0.320 AC: 354605 AN: 1106802

Other (OTH) AF: 0.314 AC: 18894 AN: 60188

GnomAD4 genome AF: 0.281 AC: 42659 AN: 151876 Hom.: 6184 Cov.: 30 AF XY: 0.278 AC XY: 20619 AN XY: 74194

African (AFR) AF: 0.230 AC: 9544 AN: 41428

American (AMR) AF: 0.264 AC: 4034 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1444 AN: 3470

East Asian (EAS) AF: 0.0838 AC: 432 AN: 5158

South Asian (SAS) AF: 0.219 AC: 1052 AN: 4804

European-Finnish (FIN) AF: 0.317 AC: 3341 AN: 10528

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21582 AN: 67916

Other (OTH) AF: 0.303 AC: 640 AN: 2110

Alfa AF: 0.316 Hom.: 1596

Bravo AF: 0.279

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.60
PhyloP100		-0.62
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: rs1265078; hg19: chr6-31112602; COSMIC: COSV52550411; COSMIC: COSV52550411;