rs1434939

Positions:

• chr8-68592027-T-A
• chr8-68592027-T-C

Variant summary

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

The NM_052958.4(C8orf34):​c.1106-48349T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,016 control chromosomes in the GnomAD database, including 8,609 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 0.33 (8609 hom., cov: 32)
• Consequence: C8orf34 NM_052958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C8orf34	NM_052958.4	c.1106-48349T>A		intron_variant		ENST00000518698.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8orf34	ENST00000518698.6	c.1106-48349T>A		intron_variant		2	NM_052958.4	P2
C8orf34	ENST00000337103.8	c.773-48349T>A		intron_variant		1
C8orf34	ENST00000521406.5	c.*239-48349T>A		intron_variant, NMD_transcript_variant		2
C8orf34	ENST00000518515.1	n.130+58878T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50156 AN: 151898 Hom.: 8604 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.361

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50182 AN: 152016 Hom.: 8609 Cov.: 32 AF XY: 0.331 AC XY: 24584 AN XY: 74268

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.358

Alfa AF: 0.348 Hom.: 1169

Bravo AF: 0.328

Asia WGS AF: 0.249 AC: 865 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.30

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: rs1434939; hg19: chr8-69504262;