rs17196989

Variant names:

• chr6-31145926-A-G
• rs17196989
• NM_001105564.2:c.1581-118T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.84).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	NM_001105564.2	MANE Select	c.1581-118T>C		intron	N/A	NP_001099034.1
	CCHCR1	NM_001394641.1		c.1608-118T>C		intron	N/A	NP_001381570.1
	CCHCR1	NM_001105563.3		c.1473-118T>C		intron	N/A	NP_001099033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCHCR1	ENST00000396268.8	TSL:1 MANE Select	c.1581-118T>C		intron	N/A	ENSP00000379566.3
	CCHCR1	ENST00000451521.6	TSL:1	c.1473-118T>C		intron	N/A	ENSP00000401039.2
	CCHCR1	ENST00000376266.9	TSL:1	c.1314-118T>C		intron	N/A	ENSP00000365442.5

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

African (AFR) AF: 0.00167 AC: 22 AN: 13194

American (AMR) AF: 0.00970 AC: 198 AN: 20416

Ashkenazi Jewish (ASJ) AF: 0.00241 AC: 35 AN: 14500

East Asian (EAS) AF: 0.000444 AC: 14 AN: 31530

South Asian (SAS) AF: 0.0243 AC: 1193 AN: 49170

European-Finnish (FIN) AF: 0.0202 AC: 753 AN: 37210

Middle Eastern (MID) AF: 0.0462 AC: 171 AN: 3698

European-Non Finnish (NFE) AF: 0.0130 AC: 3717 AN: 286548

Other (OTH) AF: 0.0114 AC: 311 AN: 27256

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

African (AFR) AF: 0.00200 AC: 83 AN: 41584

American (AMR) AF: 0.00725 AC: 111 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0194 AC: 94 AN: 4834

European-Finnish (FIN) AF: 0.0247 AC: 262 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 945 AN: 68032

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0120 Hom.: 32

Bravo AF: 0.00827

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.66
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17196989; hg19: chr6-31113703;