Genetic Variant ENST00000376266.9:c.-86T>A (chr6-31158201-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

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: Benign. The variant received -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	Effect	Protein
CCHCR1	NM_001394642.1 link	c.-202T>A	upstream_gene_variant	NP_001381571.1
CCHCR1	NM_001394643.1 link	c.-229T>A	upstream_gene_variant	NP_001381572.1
CCHCR1	NM_001394644.1 link	c.-152T>A	upstream_gene_variant	NP_001381573.1

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

25820

AN:

144384

Hom.:

2407

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.149

AC XY:

141

AN XY:

948

show subpopulations

African (AFR)

AF:

0.100

AC:

AN:

American (AMR)

AF:

0.0522

AC:

AN:

230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.150

AC:

AN:

254

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.199

AC:

214

AN:

1078

Other (OTH)

AF:

0.180

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.179

AC:

25829

AN:

144478

Hom.:

2411

Cov.:

AF XY:

0.174

AC XY:

12204

AN XY:

70048

show subpopulations

African (AFR)

AF:

0.152

AC:

5846

AN:

38440

American (AMR)

AF:

0.112

AC:

1617

AN:

14442

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

607

AN:

3394

East Asian (EAS)

AF:

0.0423

AC:

207

AN:

4888

South Asian (SAS)

AF:

0.131

AC:

586

AN:

4472

European-Finnish (FIN)

AF:

0.150

AC:

1414

AN:

9416

Middle Eastern (MID)

AF:

0.233

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.224

AC:

14856

AN:

66234

Other (OTH)

AF:

0.159

AC:

320

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1066

2132

3197

4263

5329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.188

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

(source)

DANN

Benign

0.78

PhyloP100

0.65

PromoterAI

0.069

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over