rs720465

Positions:

• chr6-31158000-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019052.4(CCHCR1):​c.-52+167G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 254,130 control chromosomes in the GnomAD database, including 10,789 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 0.29 (6607 hom., cov: 28)
  • Exomes 𝑓: 0.27 (4182 hom.)
• Consequence: CCHCR1 NM_019052.4 intron
• Scores: Splicing: ADA: 0.00007773
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865

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]

CCHCR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCHCR1	XM_017010963.2	c.-196G>T		5_prime_UTR_premature_start_codon_gain_variant	1/19		XP_016866452.1
CCHCR1	XM_017010964.2	c.-53G>T		5_prime_UTR_premature_start_codon_gain_variant	1/18		XP_016866453.1
CCHCR1	XM_047418909.1	c.-235G>T		5_prime_UTR_premature_start_codon_gain_variant	1/19		XP_047274865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000376266.9	c.-52+167G>T		intron_variant		1		ENSP00000365442.5
CCHCR1	ENST00000509552.5	n.24+171G>T		intron_variant		1
CCHCR1	ENST00000448162.6	c.-53G>T		5_prime_UTR_premature_start_codon_gain_variant	1/5	5		ENSP00000390027.2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43963 AN: 151482 Hom.: 6606 Cov.: 28

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.265 AC: 27200 AN: 102532 Hom.: 4182 Cov.: 0 AF XY: 0.265 AC XY: 14611 AN XY: 55078

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.0613

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.290 AC: 43973 AN: 151598 Hom.: 6607 Cov.: 28 AF XY: 0.282 AC XY: 20890 AN XY: 74070

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.276

Alfa AF: 0.302 Hom.: 12891

Bravo AF: 0.295

Asia WGS AF: 0.195 AC: 677 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000078
dbscSNV1_RF	Benign	0.0040
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: rs720465; hg19: chr6-31125777;