rs12194183

Variant names:

• chr6-117564796-C-T
• rs12194183
• NM_020399.4:c.1259-1412G>A

Variant summary

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

The NM_020399.4(GOPC):​c.1259-1412G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,048 control chromosomes in the GnomAD database, including 4,661 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 0.23 (4661 hom., cov: 32)
• Consequence: GOPC NM_020399.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 2 publications found

Genes affected

GOPC (HGNC:17643): (golgi associated PDZ and coiled-coil motif containing) This gene encodes a Golgi protein with a PDZ domain. The PDZ domain is globular and proteins which contain them bind other proteins through short motifs near the C-termini. Mice which are deficient in the orthologous protein have globozoospermia and are infertile. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

DCBLD1 (HGNC:21479): (discoidin, CUB and LCCL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000282218 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOPC	NM_020399.4	c.1259-1412G>A		intron_variant	Intron 8 of 8	ENST00000368498.7	NP_065132.1
DCBLD1	NM_173674.3	c.1616-4824C>T		intron_variant	Intron 14 of 14		NP_775945.1
GOPC	NM_001017408.3	c.1235-1412G>A		intron_variant	Intron 7 of 7		NP_001017408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOPC	ENST00000368498.7	c.1259-1412G>A		intron_variant	Intron 8 of 8	1	NM_020399.4	ENSP00000357484.2
ENSG00000282218	ENST00000467125.1	c.547+2058G>A		intron_variant	Intron 4 of 6	2		ENSP00000487717.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34748 AN: 151930 Hom.: 4663 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.228 AC: 34742 AN: 152048 Hom.: 4661 Cov.: 32 AF XY: 0.235 AC XY: 17492 AN XY: 74294

African (AFR) AF: 0.0958 AC: 3978 AN: 41504

American (AMR) AF: 0.214 AC: 3270 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3470

East Asian (EAS) AF: 0.168 AC: 865 AN: 5156

South Asian (SAS) AF: 0.398 AC: 1922 AN: 4824

European-Finnish (FIN) AF: 0.377 AC: 3973 AN: 10534

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19045 AN: 67964

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.272 Hom.: 3257

Bravo AF: 0.207

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.46
PhyloP100		0.051
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: rs12194183; hg19: chr6-117885959;