rs1272400

Positions:

• chr14-59445719-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000481661.1(GPR135):​c.*874+9965A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,728 control chromosomes in the GnomAD database, including 23,277 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 0.53 (23277 hom., cov: 29)
• Consequence: GPR135 ENST00000481661.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

GPR135 (HGNC:19991): (G protein-coupled receptor 135) Enables arrestin family protein binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR135	ENST00000481661.1	c.*874+9965A>G		intron_variant, NMD_transcript_variant		1		ENSP00000432696

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80478 AN: 151610 Hom.: 23230 Cov.: 29

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.531 AC: 80586 AN: 151728 Hom.: 23277 Cov.: 29 AF XY: 0.522 AC XY: 38667 AN XY: 74124

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.536

Alfa AF: 0.489 Hom.: 2428

Bravo AF: 0.555

Asia WGS AF: 0.372 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1272400; hg19: chr14-59912437;