NM_052958.4:c.1241+10949G>T

Variant names:

• chr8-68651460-G-T
• rs7825271
• NM_052958.4:c.1241+10949G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052958.4(C8orf34):​c.1241+10949G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,154 control chromosomes in the GnomAD database, including 54,056 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 0.84 (54056 hom., cov: 32)
• Consequence: C8orf34 NM_052958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8orf34	NM_052958.4	c.1241+10949G>T		intron_variant	Intron 8 of 13	ENST00000518698.6	NP_443190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8orf34	ENST00000518698.6	c.1241+10949G>T		intron_variant	Intron 8 of 13	2	NM_052958.4	ENSP00000427820.1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128147 AN: 152036 Hom.: 54014 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.843 AC: 128236 AN: 152154 Hom.: 54056 Cov.: 32 AF XY: 0.844 AC XY: 62789 AN XY: 74374

African (AFR) AF: 0.811 AC: 33628 AN: 41488

American (AMR) AF: 0.803 AC: 12269 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3018 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4470 AN: 5162

South Asian (SAS) AF: 0.872 AC: 4208 AN: 4824

European-Finnish (FIN) AF: 0.864 AC: 9163 AN: 10606

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58596 AN: 68002

Other (OTH) AF: 0.847 AC: 1791 AN: 2114

Alfa AF: 0.855 Hom.: 179568

Bravo AF: 0.837

Asia WGS AF: 0.863 AC: 3003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.42
PhyloP100		-0.13
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: rs7825271; hg19: chr8-69563695;