rs1253130

Variant names:

• chr14-59455055-G-A
• rs1253130
• ENST00000481661.1:n.*874+629C>T

Variant summary

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

The ENST00000481661.1(GPR135):​n.*874+629C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 151,428 control chromosomes in the GnomAD database, including 112 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 0.021 (112 hom., cov: 31)
• Consequence: GPR135 ENST00000481661.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR135	XM_017021596.3	c.*4317C>T		3_prime_UTR_variant	Exon 4 of 4		XP_016877085.1
GPR135	XM_017021598.3	c.*2873C>T		3_prime_UTR_variant	Exon 5 of 5		XP_016877087.1
GPR135	XM_017021599.3	c.*2773C>T		3_prime_UTR_variant	Exon 4 of 4		XP_016877088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR135	ENST00000481661.1	n.*874+629C>T		intron_variant	Intron 6 of 6	1		ENSP00000432696.1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3159 AN: 151316 Hom.: 111 Cov.: 31

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00730

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0150

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

GnomAD4 genome AF: 0.0210 AC: 3174 AN: 151428 Hom.: 112 Cov.: 31 AF XY: 0.0199 AC XY: 1475 AN XY: 73944

African (AFR) AF: 0.0728 AC: 3001 AN: 41212

American (AMR) AF: 0.00729 AC: 111 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10418

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67894

Other (OTH) AF: 0.0149 AC: 31 AN: 2086

Alfa AF: 0.0201 Hom.: 9

Bravo AF: 0.0244

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.32
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs1253130; hg19: chr14-59921773;