8-68447909-T-G

Position:

• chr8-68447909-T-G

Variant summary

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

The NM_052958.4(C8orf34):​c.607+1449T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,208 control chromosomes in the GnomAD database, including 2,498 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 0.17 (2498 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: C8orf34 NM_052958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745

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]

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 (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C8orf34	NM_052958.4	c.607+1449T>G		intron_variant		ENST00000518698.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8orf34	ENST00000518698.6	c.607+1449T>G		intron_variant		2	NM_052958.4	P2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25256 AN: 152090 Hom.: 2500 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.159

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.166 AC: 25247 AN: 152208 Hom.: 2498 Cov.: 32 AF XY: 0.168 AC XY: 12531 AN XY: 74404

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.157

Alfa AF: 0.194 Hom.: 4426

Bravo AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.63

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: rs11786594; hg19: chr8-69360144;