Genetic Variant ENST00000376266.9:c.-86T>G (chr6-31158201-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000376266.9(CCHCR1):c.-86T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCHCR1
ENST00000376266.9 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.646

Publications

14 publications found

Variant links:

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 links:

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]

TCF19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
CCHCR1	NM_001394642.1 link	c.-202T>G	upstream_gene_variant	NP_001381571.1
CCHCR1	NM_001394643.1 link	c.-229T>G	upstream_gene_variant	NP_001381572.1
CCHCR1	NM_001394644.1 link	c.-152T>G	upstream_gene_variant	NP_001381573.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CCHCR1	ENST00000376266.9 link	c.-86T>G	5_prime_UTR_variant	Exon 1 of 18	1	ENSP00000365442.5	Q8TD31-1
CCHCR1	ENST00000652427.1 link	n.-86T>G	non_coding_transcript_exon_variant	Exon 1 of 19		ENSP00000498342.1	A0A494C023
CCHCR1	ENST00000652535.1 link	n.-86T>G	non_coding_transcript_exon_variant	Exon 1 of 19		ENSP00000498479.1	A0A494C0D7

Frequencies

GnomAD3 genomes

AF:

0.0000138

AC:

AN:

144454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

950

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000138

AC:

AN:

144454

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

69972

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000261

AC:

AN:

38358

American (AMR)

AF:

0.00

AC:

AN:

14428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

4902

South Asian (SAS)

AF:

0.00

AC:

AN:

4484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66274

Other (OTH)

AF:

0.00

AC:

AN:

1988

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.65

PromoterAI

0.087

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over