rs17196989

chr6-31145926-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001105564.2(CCHCR1):c.1581-118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 635,876 control chromosomes in the GnomAD database, including 89 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 0.010 (11 hom., cov: 32)
  • Exomes 𝑓: 0.013 (78 hom.)
• Consequence: CCHCR1 NM_001105564.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0101 (1537/152354) while in subpopulation SAS AF= 0.0194 (94/4834). AF 95% confidence interval is 0.0163. There are 11 homozygotes in gnomad4. There are 788 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCHCR1	NM_001105564.2	c.1581-118T>C		intron_variant		ENST00000396268.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCHCR1	ENST00000396268.8	c.1581-118T>C		intron_variant		1	NM_001105564.2	A2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1538 AN: 152236 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0133 AC: 6414 AN: 483522 Hom.: 78 AF XY: 0.0140 AC XY: 3563 AN XY: 254850

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.00970

Gnomad4 ASJ exome AF: 0.00241

Gnomad4 EAS exome AF: 0.000444

Gnomad4 SAS exome AF: 0.0243

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0101 AC: 1537 AN: 152354 Hom.: 11 Cov.: 32 AF XY: 0.0106 AC XY: 788 AN XY: 74504

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0194

Gnomad4 FIN AF: 0.0247

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0123 Hom.: 15

Bravo AF: 0.00827

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.1
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs17196989; hg19: chr6-31113703;