chr14-59445719-T-C

Variant names:

• chr14-59445719-T-C
• rs1272400
• ENST00000481661.1:n.*874+9965A>G

Variant summary

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

The ENST00000481661.1(GPR135):​n.*874+9965A>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR135	ENST00000481661.1	n.*874+9965A>G		intron_variant	Intron 6 of 6	1		ENSP00000432696.1

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

African (AFR) AF: 0.758 AC: 31349 AN: 41342

American (AMR) AF: 0.524 AC: 7996 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2268 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1055 AN: 5136

South Asian (SAS) AF: 0.482 AC: 2309 AN: 4790

European-Finnish (FIN) AF: 0.321 AC: 3385 AN: 10536

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30511 AN: 67906

Other (OTH) AF: 0.536 AC: 1126 AN: 2100

Alfa AF: 0.499 Hom.: 2647

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
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs1272400; hg19: chr14-59912437;