chr12-12715767-C-T

Position:

• 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: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]

CDKN1B (HGNC:):

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		intron_variant		3
CDKN1B	ENST00000682620.1	n.1631-3058C>T		intron_variant
CDKN1B	ENST00000684771.1	n.585-3058C>T		intron_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;