rs36228499

Variant names:

Variant summary

Our verdict is The variant received -16 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Strong

The XM_011520623.4(GPR19):c.-1496G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Note: XM_011520623.4 is not a MANE Select or MANE Plus Clinical transcript for GPR19; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.429 (AC=427,675) in the gnomAD database across 996,668 control chromosomes, including 93,107 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.448. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12128 hom., cov: 33)

Exomes 𝑓: 0.44 ( 80979 hom. )

Consequence

GPR19
XM_011520623.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.177

Publications

20 publications found

Variant links:

Genes affected

GPR19 (HGNC:4473): (G protein-coupled receptor 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

GPR19 links:

CDKN1B (HGNC:1785): (cyclin dependent kinase inhibitor 1B) This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4). [provided by RefSeq, Apr 2014]

CDKN1B Gene-Disease associations (from GenCC):

multiple endocrine neoplasia type 4
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
multiple endocrine neoplasia
Inheritance: AD Classification: STRONG Submitted by: G2P
hereditary nonpolyposis colon cancer
Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

CDKN1B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript XM_011520623.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -16 points.

Show applied only (3)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4484 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000477087.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CDKN1B	ENST00000477087.1	TSL:3	n.154+1119C>A	intron	N/A
CDKN1B	ENST00000682620.1		n.1631-1823C>A	intron	N/A
CDKN1B	ENST00000684771.1		n.585-1823C>A	intron	N/A

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.387	AC:58806	Hom:12127	AN:152010	Cov:33
GnomAD4 exome	AF: 0.437	AC:368860	Hom:80979	AN:844544	Cov:31
GnomAD4 genome	AF: 0.387	AC:58815	Hom:12128	AN:152124	Cov:33
TOPMed (Bravo)	AF: 0.373	AC:98765	Hom:19700	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.415	AC:10296	Hom:2281	AN:24820	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.365	AC:855	Hom:155	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.447	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.517	AC:155	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.391	AC:1356	Hom:	AN:3472	Cov:
Korea4K (4,157 Koreans)	AF: 0.451	AC:3236	Hom:	AN:7174	Cov:
Qatari Genome	AF: 0.284	AC:50	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.458	AC:55962	Hom:12797	AN:122148	Cov:
Turkish Variome	AF: 0.456	AC:704	Hom:160	AN:1544	Cov:
UK10K	AF: 0.439	AC:3319	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.436	AC:3911	Hom:851	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	AF	AC	AN	AF	AC	AN
SCHEMA (Schizophrenia)	0.140	3351	23966	0.0773	2355	30482

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Multiple endocrine neoplasia type 4 (1)

not provided (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	3.4
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.7
DANN	Benign	0.90
GPN-Star LLR	N/A	-1.5
GPN-Star score	N/A	1.5
PhyloP100	Benign	-0.18
PromoterAI	N/A	-0.043	Neutral

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over