rs35756741

Positions:

• chr12-12715767-C-T

Variant summary

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

The XM_011520623.4(GPR19):​c.-261G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 152,260 control chromosomes in the GnomAD database, including 502 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 0.070 (502 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: GPR19 XM_011520623.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

Genes affected

GPR19 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR19	XM_011520623.4	c.-261G>A		5_prime_UTR_variant	1/4		XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000477087.1	n.48-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3
CDKN1B	ENST00000682620.1	n.1631-3058C>T		intron_variant, non_coding_transcript_variant
CDKN1B	ENST00000684771.1	n.585-3058C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10698 AN: 152118 Hom.: 498 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0705

GnomAD4 exome AF: 0.250 AC: 6 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0703 AC: 10709 AN: 152236 Hom.: 502 Cov.: 32 AF XY: 0.0711 AC XY: 5293 AN XY: 74412

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.00327

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0917

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.0767 Hom.: 61

Bravo AF: 0.0636

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.8
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35756741; hg19: chr12-12868701;