8-68818484-A-T

Position:

• chr8-68818484-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052958.4(C8orf34):​c.*238A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 470,834 control chromosomes in the GnomAD database, including 7,039 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 0.15 (1858 hom., cov: 32)
  • Exomes 𝑓: 0.16 (5181 hom.)
• Consequence: C8orf34 NM_052958.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C8orf34	NM_052958.4	c.*238A>T		3_prime_UTR_variant	14/14	ENST00000518698.6	NP_443190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C8orf34	ENST00000518698.6	c.*238A>T		3_prime_UTR_variant	14/14	2	NM_052958.4	ENSP00000427820.1
C8orf34	ENST00000337103.8	c.*238A>T		3_prime_UTR_variant	13/13	1		ENSP00000337174.4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22327 AN: 151940 Hom.: 1859 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.159 AC: 50549 AN: 318778 Hom.: 5181 Cov.: 0 AF XY: 0.160 AC XY: 26276 AN XY: 164328

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.147 AC: 22332 AN: 152056 Hom.: 1858 Cov.: 32 AF XY: 0.152 AC XY: 11295 AN XY: 74362

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.140

Alfa AF: 0.142 Hom.: 203

Bravo AF: 0.139

Asia WGS AF: 0.333 AC: 1154 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs16935110; hg19: chr8-69730719; COSMIC: COSV61401679; COSMIC: COSV61401679;