chr8-68592027-T-A

Variant names:

• chr8-68592027-T-A
• rs1434939
• NM_052958.4:c.1106-48349T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
C8orf34	NM_052958.4	c.1106-48349T>A		intron_variant	Intron 7 of 13	ENST00000518698.6	NP_443190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8orf34	ENST00000518698.6	c.1106-48349T>A		intron_variant	Intron 7 of 13	2	NM_052958.4	ENSP00000427820.1
C8orf34	ENST00000337103.8	c.773-48349T>A		intron_variant	Intron 6 of 12	1		ENSP00000337174.4
C8orf34	ENST00000518515.1	n.130+58878T>A		intron_variant	Intron 1 of 3	3
C8orf34	ENST00000521406.5	n.*239-48349T>A		intron_variant	Intron 7 of 13	2		ENSP00000429081.1

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

African (AFR) AF: 0.230 AC: 9549 AN: 41492

American (AMR) AF: 0.353 AC: 5393 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3470

East Asian (EAS) AF: 0.288 AC: 1489 AN: 5162

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4820

European-Finnish (FIN) AF: 0.374 AC: 3944 AN: 10540

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25816 AN: 67960

Other (OTH) AF: 0.358 AC: 754 AN: 2108

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
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1434939; hg19: chr8-69504262;