14-88006251-C-T

Variant names:

• chr14-88006251-C-T
• rs8005161
• NM_003608.4:c.-460+1029C>T

Variant summary

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

The NM_003608.4(GPR65):​c.-460+1029C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,148 control chromosomes in the GnomAD database, including 3,655 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 (3655 hom., cov: 33)
• Consequence: GPR65 NM_003608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 67 publications found

Genes affected

GPR65 (HGNC:4517): (G protein-coupled receptor 65) Enables G protein-coupled receptor activity. Involved in several processes, including actin cytoskeleton reorganization; activation of GTPase activity; and positive regulation of stress fiber assembly. Located in 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR65	NM_003608.4	c.-460+1029C>T		intron_variant	Intron 1 of 1	ENST00000267549.5	NP_003599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR65	ENST00000267549.5	c.-460+1029C>T		intron_variant	Intron 1 of 1	1	NM_003608.4	ENSP00000267549.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27447 AN: 152030 Hom.: 3642 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.181 AC: 27503 AN: 152148 Hom.: 3655 Cov.: 33 AF XY: 0.179 AC XY: 13337 AN XY: 74374

African (AFR) AF: 0.371 AC: 15373 AN: 41480

American (AMR) AF: 0.161 AC: 2454 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3470

East Asian (EAS) AF: 0.160 AC: 828 AN: 5178

South Asian (SAS) AF: 0.268 AC: 1290 AN: 4818

European-Finnish (FIN) AF: 0.0785 AC: 832 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0888 AC: 6042 AN: 68018

Other (OTH) AF: 0.162 AC: 343 AN: 2112

Alfa AF: 0.119 Hom.: 4746

Bravo AF: 0.191

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.035
DANN	Benign	0.65
PhyloP100		-2.3
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: rs8005161; hg19: chr14-88472595;