6-31150242-T-C

Variant names:

• chr6-31150242-T-C
• rs1265112
• NM_001105564.2:c.1213-27A>G

Variant summary

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

The NM_001105564.2(CCHCR1):​c.1213-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,609,614 control chromosomes in the GnomAD database, including 76,978 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 (6197 hom., cov: 32)
  • Exomes 𝑓: 0.31 (70781 hom.)
• Consequence: CCHCR1 NM_001105564.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 67 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=-0.74).
• 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: 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.1213-27A>G		intron	N/A	NP_001099034.1	Q8TD31-2
	CCHCR1	NM_001394641.1		c.1240-27A>G		intron	N/A	NP_001381570.1
	CCHCR1	NM_001105563.3		c.1105-27A>G		intron	N/A	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.1213-27A>G		intron	N/A	ENSP00000379566.3	Q8TD31-2
	CCHCR1	ENST00000451521.6	TSL:1	c.1105-27A>G		intron	N/A	ENSP00000401039.2	Q8TD31-3
	CCHCR1	ENST00000376266.9	TSL:1	c.946-27A>G		intron	N/A	ENSP00000365442.5	Q8TD31-1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42727 AN: 151960 Hom.: 6198 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.278 AC: 69159 AN: 248440 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: 0.0770

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.306 AC: 446062 AN: 1457536 Hom.: 70781 Cov.: 33 AF XY: 0.304 AC XY: 220682 AN XY: 724988

African (AFR) AF: 0.228 AC: 7617 AN: 33406

American (AMR) AF: 0.276 AC: 12281 AN: 44428

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11469 AN: 26082

East Asian (EAS) AF: 0.0681 AC: 2701 AN: 39660

South Asian (SAS) AF: 0.237 AC: 20381 AN: 86068

European-Finnish (FIN) AF: 0.302 AC: 16089 AN: 53332

Middle Eastern (MID) AF: 0.335 AC: 1850 AN: 5520

European-Non Finnish (NFE) AF: 0.320 AC: 354788 AN: 1108812

Other (OTH) AF: 0.314 AC: 18886 AN: 60228

GnomAD4 genome AF: 0.281 AC: 42744 AN: 152078 Hom.: 6197 Cov.: 32 AF XY: 0.278 AC XY: 20675 AN XY: 74344

African (AFR) AF: 0.231 AC: 9569 AN: 41478

American (AMR) AF: 0.265 AC: 4044 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3470

East Asian (EAS) AF: 0.0833 AC: 431 AN: 5172

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4816

European-Finnish (FIN) AF: 0.317 AC: 3357 AN: 10582

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21608 AN: 67958

Other (OTH) AF: 0.303 AC: 640 AN: 2112

Alfa AF: 0.307 Hom.: 31932

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	-0.74
CADD	Benign	6.6
DANN	Benign	0.86
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1265112; hg19: chr6-31118019; COSMIC: COSV66185490; COSMIC: COSV66185490;