rs11550615

Variant names:

• chr12-12717469-C-G
• rs11550615
• NM_004064.5:c.-371C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-12717469-C-G
• chr12-12717469-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004064.5(CDKN1B):​c.-371C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,329,686 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CDKN1B NM_004064.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 1 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1B	NM_004064.5	c.-371C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000228872.9	NP_004055.1
CDKN1B	NM_004064.5	c.-371C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000228872.9	NP_004055.1
GPR19	XM_011520623.4	c.-1963G>C		upstream_gene_variant			XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000228872.9	c.-371C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	NM_004064.5	ENSP00000228872.4
CDKN1B	ENST00000228872.9	c.-371C>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_004064.5	ENSP00000228872.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152276 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000170 AC: 2 AN: 1177410 Hom.: 0 Cov.: 35 AF XY: 0.00000177 AC XY: 1 AN XY: 564438

African (AFR) AF: 0.00 AC: 0 AN: 26280

American (AMR) AF: 0.00 AC: 0 AN: 14132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16446

East Asian (EAS) AF: 0.00 AC: 0 AN: 26666

South Asian (SAS) AF: 0.00 AC: 0 AN: 55470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3164

European-Non Finnish (NFE) AF: 0.00000207 AC: 2 AN: 968302

Other (OTH) AF: 0.00 AC: 0 AN: 47558

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152276 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74400

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68054

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.68
PhyloP100		0.020
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11550615; hg19: chr12-12870403;