6-31158201-A-T

Variant names:

• chr6-31158201-A-T
• rs3130455
• ENST00000376266.9:c.-86T>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000376266.9(CCHCR1):​c.-86T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 146,138 control chromosomes in the GnomAD database, including 2,444 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 0.18 (2411 hom., cov: 30)
  • Exomes 𝑓: 0.17 (33 hom.)
• Consequence: CCHCR1 ENST00000376266.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646

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]

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCHCR1	NM_001394642.1	c.-202T>A		upstream_gene_variant			NP_001381571.1
CCHCR1	NM_001394643.1	c.-229T>A		upstream_gene_variant			NP_001381572.1
CCHCR1	NM_001394644.1	c.-152T>A		upstream_gene_variant			NP_001381573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000376266.9	c.-86T>A		5_prime_UTR_variant	Exon 1 of 18	1		ENSP00000365442.5
CCHCR1	ENST00000396263.6	c.-152T>A		5_prime_UTR_variant	Exon 1 of 16	5		ENSP00000379561.2
CCHCR1	ENST00000448141.6	c.-82T>A		5_prime_UTR_variant	Exon 1 of 5	3		ENSP00000414323.2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 25820 AN: 144384 Hom.: 2407 Cov.: 30

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.167 AC: 277 AN: 1660 Hom.: 33 Cov.: 0 AF XY: 0.149 AC XY: 141 AN XY: 948

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.0522

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.179 AC: 25829 AN: 144478 Hom.: 2411 Cov.: 30 AF XY: 0.174 AC XY: 12204 AN XY: 70048

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0423

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.159

Alfa AF: 0.188 Hom.: 410

Bravo AF: 0.168

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3130455; hg19: chr6-31125978;