NM_001291549.3:c.97+258G>C

Variant names:

• chr6-36678191-G-C
• rs730506
• ENST00000864200.1:c.-28G>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+258G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 335,600 control chromosomes in the GnomAD database, including 7,895 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 (3672 hom., cov: 32)
  • Exomes 𝑓: 0.21 (4223 hom.)
• Consequence: CDKN1A NM_001291549.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 16 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=-0.82).
• 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+258G>C		intron	N/A	NP_001278478.1
	CDKN1A	NM_001374509.1		c.97+258G>C		intron	N/A	NP_001361438.1
	CDKN1A	NM_001374510.1		c.34+1621G>C		intron	N/A	NP_001361439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	ENST00000864200.1		c.-28G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000534259.1
	CDKN1A	ENST00000864200.1		c.-28G>C		5_prime_UTR	Exon 1 of 3	ENSP00000534259.1
	CDKN1A	ENST00000448526.6	TSL:3	c.-6+258G>C		intron	N/A	ENSP00000409259.3	P38936

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33123 AN: 152018 Hom.: 3663 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: 0.299

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.206 AC: 37815 AN: 183464 Hom.: 4223 Cov.: 0 AF XY: 0.217 AC XY: 21705 AN XY: 100098

African (AFR) AF: 0.253 AC: 1133 AN: 4470

American (AMR) AF: 0.154 AC: 1310 AN: 8498

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 1157 AN: 4502

East Asian (EAS) AF: 0.112 AC: 927 AN: 8306

South Asian (SAS) AF: 0.278 AC: 10091 AN: 36274

European-Finnish (FIN) AF: 0.164 AC: 1275 AN: 7778

Middle Eastern (MID) AF: 0.230 AC: 150 AN: 652

European-Non Finnish (NFE) AF: 0.191 AC: 19821 AN: 103860

Other (OTH) AF: 0.214 AC: 1951 AN: 9124

GnomAD4 genome AF: 0.218 AC: 33146 AN: 152136 Hom.: 3672 Cov.: 32 AF XY: 0.217 AC XY: 16107 AN XY: 74362

African (AFR) AF: 0.260 AC: 10778 AN: 41486

American (AMR) AF: 0.198 AC: 3030 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3472

East Asian (EAS) AF: 0.129 AC: 666 AN: 5178

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

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10584

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13720 AN: 67994

Other (OTH) AF: 0.259 AC: 546 AN: 2106

Alfa AF: 0.208 Hom.: 404

Bravo AF: 0.218

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.72
PhyloP100		0.32
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: rs730506; hg19: chr6-36645968;