rs3176447

Positions:

• chr1-50968015-T-A
• chr1-50968015-T-C

Variant summary

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

The XM_047437269.1(LOC124904176):​c.*969A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,354 control chromosomes in the GnomAD database, including 520 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 0.078 (520 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LOC124904176 XM_047437269.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

Genes affected

LOC124904176 (HGNC:):

CDKN2C (HGNC:1789): (cyclin dependent kinase inhibitor 2C) The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to interact with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. Ectopic expression of this gene was shown to suppress the growth of human cells in a manner that appears to correlate with the presence of a wild-type RB1 function. Studies in the knockout mice suggested the roles of this gene in regulating spermatogenesis, as well as in suppressing tumorigenesis. Two alternatively spliced transcript variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904176	XM_047437269.1	c.*969A>T		3_prime_UTR_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000702980.1	n.538A>T		non_coding_transcript_exon_variant	1/1
CDKN2C	ENST00000262662.5	c.-1896T>A		5_prime_UTR_variant	2/4	2		P1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11822 AN: 152234 Hom.: 518 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0759

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0777 AC: 11834 AN: 152354 Hom.: 520 Cov.: 33 AF XY: 0.0756 AC XY: 5629 AN XY: 74504

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.0803

Alfa AF: 0.0323 Hom.: 21

Bravo AF: 0.0789

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs3176447; hg19: chr1-51433687;