rs16935110

Variant names:

• chr8-68818484-A-T
• rs16935110
• NM_052958.4:c.*238A>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.*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
• Publications: 7 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=-0.9).
• 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 rank	MANE	Protein	UniProt
C8orf34	NM_052958.4	c.*238A>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000518698.6	NP_443190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8orf34	ENST00000518698.6	c.*238A>T		3_prime_UTR_variant	Exon 14 of 14	2	NM_052958.4	ENSP00000427820.1
C8orf34	ENST00000337103.8	c.*238A>T		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000337174.4
C8orf34	ENST00000521406.5	n.*988A>T		downstream_gene_variant		2		ENSP00000429081.1

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

African (AFR) AF: 0.106 AC: 1064 AN: 10026

American (AMR) AF: 0.116 AC: 1441 AN: 12422

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 1499 AN: 10418

East Asian (EAS) AF: 0.428 AC: 11262 AN: 26286

South Asian (SAS) AF: 0.221 AC: 3273 AN: 14840

European-Finnish (FIN) AF: 0.155 AC: 4778 AN: 30882

Middle Eastern (MID) AF: 0.120 AC: 173 AN: 1440

European-Non Finnish (NFE) AF: 0.125 AC: 24184 AN: 193182

Other (OTH) AF: 0.149 AC: 2875 AN: 19282

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

African (AFR) AF: 0.124 AC: 5160 AN: 41496

American (AMR) AF: 0.124 AC: 1889 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2203 AN: 5152

South Asian (SAS) AF: 0.271 AC: 1304 AN: 4820

European-Finnish (FIN) AF: 0.163 AC: 1727 AN: 10582

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9020 AN: 67972

Other (OTH) AF: 0.140 AC: 294 AN: 2100

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
PhyloP100		0.56
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: rs16935110; hg19: chr8-69730719; COSMIC: COSV61401679; COSMIC: COSV61401679;