rs17378130

Variant names:

• chr8-123229102-C-T
• rs17378130
• NM_032847.3:c.815+2198G>A

Variant summary

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

The NM_032847.3(C8orf76):​c.815+2198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 151,878 control chromosomes in the GnomAD database, including 735 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 0.085 (735 hom., cov: 32)
• Consequence: C8orf76 NM_032847.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 4 publications found

Genes affected

C8orf76 (HGNC:25924): (chromosome 8 open reading frame 76)

ZHX1-C8orf76 (HGNC:42975): (ZHX1-C8orf76 readthrough) This locus represents naturally occurring read-through transcription between the neighboring zinc fingers and homeoboxes 1 (ZHX1) and chromosome 8 open reading frame 76 (C8orf76) genes. The read-through transcript encodes a protein that shares sequence identity with the downstream gene, but it has a distinct N-terminus encoded by exon structure from the upstream gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032847.3. 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
	C8orf76	NM_032847.3	MANE Select	c.815+2198G>A		intron	N/A	NP_116236.1
	ZHX1-C8orf76	NM_001204180.2		c.719+2198G>A		intron	N/A	NP_001191109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8orf76	ENST00000276704.6	TSL:1 MANE Select	c.815+2198G>A		intron	N/A	ENSP00000276704.4
	ZHX1-C8orf76	ENST00000357082.8	TSL:2	c.719+2198G>A		intron	N/A	ENSP00000349593.4
	C8orf76	ENST00000517760.1	TSL:2	n.293+2198G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12849 AN: 151760 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0957

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

GnomAD4 genome AF: 0.0846 AC: 12846 AN: 151878 Hom.: 735 Cov.: 32 AF XY: 0.0829 AC XY: 6155 AN XY: 74276

African (AFR) AF: 0.0224 AC: 927 AN: 41388

American (AMR) AF: 0.0690 AC: 1048 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0545 AC: 263 AN: 4830

European-Finnish (FIN) AF: 0.106 AC: 1127 AN: 10616

Middle Eastern (MID) AF: 0.143 AC: 40 AN: 280

European-Non Finnish (NFE) AF: 0.126 AC: 8566 AN: 67926

Other (OTH) AF: 0.0946 AC: 198 AN: 2092

Alfa AF: 0.107 Hom.: 1898

Bravo AF: 0.0796

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.81
PhyloP100		-0.0050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17378130; hg19: chr8-124241342;