rs3829963

Variant names:

• chr6-36676609-C-A
• rs3829963
• ENST00000911808.1:c.-1330C>A

Variant summary

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

The NM_001291549.3(CDKN1A):​c.-142+39C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,110 control chromosomes in the GnomAD database, including 4,076 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 0.21 (4074 hom., cov: 32)
  • Exomes 𝑓: 0.24 (2 hom.)
• Consequence: CDKN1A NM_001291549.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 24 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 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.-142+39C>A		intron	N/A	NP_001278478.1
	CDKN1A	NM_001374509.1		c.-50+39C>A		intron	N/A	NP_001361438.1
	CDKN1A	NM_001374510.1		c.34+39C>A		intron	N/A	NP_001361439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	ENST00000911808.1		c.-1330C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000581867.1
	CDKN1A	ENST00000911808.1		c.-1330C>A		5_prime_UTR	Exon 1 of 3	ENSP00000581867.1
	CDKN1A	ENST00000448526.6	TSL:3	c.-38+85C>A		intron	N/A	ENSP00000409259.3	P38936

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31664 AN: 151956 Hom.: 4065 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.237 AC: 9 AN: 38 Hom.: 2 Cov.: 0 AF XY: 0.214 AC XY: 6 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 3 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.208 AC: 5 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.208 AC: 31706 AN: 152072 Hom.: 4074 Cov.: 32 AF XY: 0.209 AC XY: 15568 AN XY: 74334

African (AFR) AF: 0.314 AC: 13001 AN: 41446

American (AMR) AF: 0.302 AC: 4612 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 288 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2118 AN: 5166

South Asian (SAS) AF: 0.119 AC: 573 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1251 AN: 10592

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9281 AN: 67988

Other (OTH) AF: 0.198 AC: 418 AN: 2110

Alfa AF: 0.149 Hom.: 1565

Bravo AF: 0.234

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.71
PhyloP100		0.11
PromoterAI		-0.051	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3829963; hg19: chr6-36644386;