8-68447909-T-G

Variant names:

• chr8-68447909-T-G
• rs11786594
• NM_052958.4:c.607+1449T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052958.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8orf34	NM_052958.4	MANE Select	c.607+1449T>G		intron	N/A	NP_443190.2
	C8orf34	NM_001349476.1		c.607+1449T>G		intron	N/A	NP_001336405.1
	C8orf34	NM_001349477.1		c.607+1449T>G		intron	N/A	NP_001336406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8orf34	ENST00000518698.6	TSL:2 MANE Select	c.607+1449T>G		intron	N/A	ENSP00000427820.1
	C8orf34	ENST00000337103.8	TSL:1	c.274+1449T>G		intron	N/A	ENSP00000337174.4
	C8orf34	ENST00000348340.6	TSL:1	c.349+1449T>G		intron	N/A	ENSP00000345255.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0545 AC: 2263 AN: 41542

American (AMR) AF: 0.214 AC: 3278 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3472

East Asian (EAS) AF: 0.120 AC: 620 AN: 5182

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4824

European-Finnish (FIN) AF: 0.262 AC: 2771 AN: 10588

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14339 AN: 68002

Other (OTH) AF: 0.157 AC: 331 AN: 2110

Alfa AF: 0.186 Hom.: 6967

Bravo AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.63
PhyloP100		0.74
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: rs11786594; hg19: chr8-69360144;