NM_001105564.2:c.1739+11G>T

Variant names:

• chr6-31145437-C-A
• rs1265074
• NM_001105564.2:c.1739+11G>T

Variant summary

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

The NM_001105564.2(CCHCR1):​c.1739+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,692 control chromosomes in the GnomAD database, including 35,959 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 0.21 (3496 hom., cov: 33)
  • Exomes 𝑓: 0.21 (32463 hom.)
• Consequence: CCHCR1 NM_001105564.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.848
• Publications: 30 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 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.1739+11G>T		intron	N/A	NP_001099034.1
	CCHCR1	NM_001394641.1		c.1766+11G>T		intron	N/A	NP_001381570.1
	CCHCR1	NM_001105563.3		c.1631+11G>T		intron	N/A	NP_001099033.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.1739+11G>T		intron	N/A	ENSP00000379566.3
	CCHCR1	ENST00000451521.6	TSL:1	c.1631+11G>T		intron	N/A	ENSP00000401039.2
	CCHCR1	ENST00000376266.9	TSL:1	c.1472+11G>T		intron	N/A	ENSP00000365442.5

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31951 AN: 151978 Hom.: 3495 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.228 AC: 57373 AN: 251426 AF XY: 0.225

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.0982

Gnomad EAS exome AF: 0.334

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.206 AC: 300787 AN: 1461596 Hom.: 32463 Cov.: 44 AF XY: 0.206 AC XY: 149482 AN XY: 727114

African (AFR) AF: 0.191 AC: 6378 AN: 33476

American (AMR) AF: 0.309 AC: 13814 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2679 AN: 26136

East Asian (EAS) AF: 0.340 AC: 13483 AN: 39700

South Asian (SAS) AF: 0.243 AC: 20998 AN: 86250

European-Finnish (FIN) AF: 0.229 AC: 12233 AN: 53420

Middle Eastern (MID) AF: 0.199 AC: 1141 AN: 5748

European-Non Finnish (NFE) AF: 0.196 AC: 218365 AN: 1111756

Other (OTH) AF: 0.194 AC: 11696 AN: 60388

GnomAD4 genome AF: 0.210 AC: 31966 AN: 152096 Hom.: 3496 Cov.: 33 AF XY: 0.214 AC XY: 15913 AN XY: 74360

African (AFR) AF: 0.195 AC: 8083 AN: 41464

American (AMR) AF: 0.286 AC: 4377 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1763 AN: 5164

South Asian (SAS) AF: 0.243 AC: 1175 AN: 4826

European-Finnish (FIN) AF: 0.224 AC: 2373 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13268 AN: 67986

Other (OTH) AF: 0.192 AC: 403 AN: 2104

Alfa AF: 0.197 Hom.: 5521

Bravo AF: 0.214

Asia WGS AF: 0.312 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Benign	0.84
PhyloP100		0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1265074; hg19: chr6-31113214; COSMIC: COSV66185689; COSMIC: COSV66185689;