ENST00000503448.1:n.220-2364C>T

Variant names:

• chr4-8578031-C-T
• rs1282
• ENST00000503448.1:n.220-2364C>T

Variant summary

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

The ENST00000503448.1(GPR78):​n.220-2364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,074 control chromosomes in the GnomAD database, including 2,448 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 0.18 (2448 hom., cov: 32)
• Consequence: GPR78 ENST00000503448.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 7 publications found

Genes affected

GPR78 (HGNC:4528): (G protein-coupled receptor 78) The protein encoded by this gene belongs to the G protein-coupled receptor family, which contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. This is an orphan receptor, which displays significant level of constitutive activity. Association analysis shows preliminary evidence for the involvement of this gene in susceptibility to bipolar affective disorder and schizophrenia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR78	ENST00000503448.1	n.220-2364C>T		intron_variant	Intron 2 of 2	4
GPR78	ENST00000503981.1	n.375-2364C>T		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26892 AN: 151956 Hom.: 2457 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.177 AC: 26895 AN: 152074 Hom.: 2448 Cov.: 32 AF XY: 0.174 AC XY: 12916 AN XY: 74344

African (AFR) AF: 0.192 AC: 7962 AN: 41468

American (AMR) AF: 0.150 AC: 2285 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3470

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5190

South Asian (SAS) AF: 0.200 AC: 962 AN: 4816

European-Finnish (FIN) AF: 0.123 AC: 1295 AN: 10564

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12815 AN: 67986

Other (OTH) AF: 0.207 AC: 436 AN: 2110

Alfa AF: 0.183 Hom.: 9058

Bravo AF: 0.177

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.19
PhyloP100		0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1282; hg19: chr4-8579758;