Variant chr8-68721358-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052958.4(C8orf34):c.1328-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,594,094 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 16 hom. )

Consequence

C8orf34
NM_052958.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002277

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0210

Variant links:

Genes affected

C8orf34 (HGNC:30905): (chromosome 8 open reading frame 34) This gene encodes a protein that is related to the cyclic AMP dependent protein kinase regulators. Naturally occurring mutations in this gene are associated with an increased risk for severe toxicities, such as diarrhea and neutropenia, in patients undergoing chemotherapeutic treatment. [provided by RefSeq, Mar 2017]

C8orf34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 8-68721358-T-C is Benign according to our data. Variant chr8-68721358-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3024951.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C8orf34	NM_052958.4 linkuse as main transcript	c.1328-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000518698.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8orf34	ENST00000518698.6 linkuse as main transcript	c.1328-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_052958.4	P2	Q49A92-6

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.000984

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00168

AC:

412

AN:

244750

Hom.:

AF XY:

0.00198

AC XY:

262

AN XY:

132538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000448

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00487

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000553

Gnomad OTH exome

AF:

0.00283

GnomAD4 exome

AF:

0.000889

AC:

1282

AN:

1442016

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

767

AN XY:

717968

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.000435

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00501

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000262

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152078

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000983

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00143

Asia WGS

AF:

0.00464

AC:

AN:

3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

C8orf34: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.4

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.018

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over