NM_001291549.3:c.97+278G>C

Variant names:

• chr6-36678211-G-C
• rs4151702
• ENST00000864200.1:c.-8G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291549.3(CDKN1A):​c.97+278G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 277,810 control chromosomes in the GnomAD database, including 7,018 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 0.22 (3667 hom., cov: 32)
  • Exomes 𝑓: 0.25 (3351 hom.)
• Consequence: CDKN1A NM_001291549.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 14 publications found

Genes affected

CDKN1A (HGNC:1784): (cyclin dependent kinase inhibitor 1A) This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]

DINOL (HGNC:53146): (damage induced long noncoding RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291549.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	NM_001291549.3		c.97+278G>C		intron	N/A	NP_001278478.1
	CDKN1A	NM_001374509.1		c.97+278G>C		intron	N/A	NP_001361438.1
	CDKN1A	NM_001374510.1		c.34+1641G>C		intron	N/A	NP_001361439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	ENST00000864200.1		c.-8G>C		splice_region	Exon 1 of 3	ENSP00000534259.1
	CDKN1A	ENST00000864200.1		c.-8G>C		5_prime_UTR	Exon 1 of 3	ENSP00000534259.1
	CDKN1A	ENST00000448526.6	TSL:3	c.-6+278G>C		intron	N/A	ENSP00000409259.3	P38936

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33122 AN: 151958 Hom.: 3658 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.249 AC: 31368 AN: 125734 Hom.: 3351 Cov.: 0 AF XY: 0.262 AC XY: 18018 AN XY: 68818

African (AFR) AF: 0.319 AC: 894 AN: 2802

American (AMR) AF: 0.200 AC: 1016 AN: 5074

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 926 AN: 3206

East Asian (EAS) AF: 0.143 AC: 673 AN: 4696

South Asian (SAS) AF: 0.329 AC: 8369 AN: 25402

European-Finnish (FIN) AF: 0.210 AC: 1083 AN: 5146

Middle Eastern (MID) AF: 0.265 AC: 129 AN: 486

European-Non Finnish (NFE) AF: 0.230 AC: 16655 AN: 72538

Other (OTH) AF: 0.254 AC: 1623 AN: 6384

GnomAD4 genome AF: 0.218 AC: 33145 AN: 152076 Hom.: 3667 Cov.: 32 AF XY: 0.217 AC XY: 16111 AN XY: 74338

African (AFR) AF: 0.260 AC: 10767 AN: 41462

American (AMR) AF: 0.198 AC: 3034 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3470

East Asian (EAS) AF: 0.129 AC: 665 AN: 5166

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4822

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10576

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13723 AN: 67980

Other (OTH) AF: 0.260 AC: 548 AN: 2110

Alfa AF: 0.200 Hom.: 379

Bravo AF: 0.218

Asia WGS AF: 0.261 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.37
PhyloP100		2.1
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4151702; hg19: chr6-36645988;