rs720465

Variant names:

• chr6-31158000-C-A
• rs720465
• ENST00000376266.9:c.-52+167G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019052.4. 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_001394642.1		c.-168+167G>T		intron	N/A	NP_001381571.1
	CCHCR1	NM_001394643.1		c.-195+167G>T		intron	N/A	NP_001381572.1
	CCHCR1	NM_001394644.1		c.-118+167G>T		intron	N/A	NP_001381573.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000376266.9	TSL:1	c.-52+167G>T		intron	N/A	ENSP00000365442.5
	CCHCR1	ENST00000509552.5	TSL:1	n.24+171G>T		intron	N/A
	CCHCR1	ENST00000448162.6	TSL:5	c.-53G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 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

African (AFR) AF: 0.298 AC: 964 AN: 3232

American (AMR) AF: 0.238 AC: 1157 AN: 4852

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 925 AN: 2822

East Asian (EAS) AF: 0.0613 AC: 358 AN: 5840

South Asian (SAS) AF: 0.261 AC: 4144 AN: 15868

European-Finnish (FIN) AF: 0.245 AC: 937 AN: 3824

Middle Eastern (MID) AF: 0.247 AC: 97 AN: 392

European-Non Finnish (NFE) AF: 0.284 AC: 17112 AN: 60350

Other (OTH) AF: 0.281 AC: 1506 AN: 5352

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

African (AFR) AF: 0.320 AC: 13178 AN: 41232

American (AMR) AF: 0.243 AC: 3711 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3468

East Asian (EAS) AF: 0.0799 AC: 413 AN: 5172

South Asian (SAS) AF: 0.251 AC: 1203 AN: 4790

European-Finnish (FIN) AF: 0.228 AC: 2404 AN: 10530

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20905 AN: 67852

Other (OTH) AF: 0.276 AC: 580 AN: 2098

Alfa AF: 0.302 Hom.: 29347

Bravo AF: 0.295

Asia WGS AF: 0.195 AC: 677 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.59
PhyloP100		0.86
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs720465; hg19: chr6-31125777;