6-36676721-T-C

Variant names:

• chr6-36676721-T-C
• rs3829964
• NM_001291549.3:c.-142+151T>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.-142+151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,986 control chromosomes in the GnomAD database, including 29,024 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 0.60 (29024 hom., cov: 31)
• Consequence: CDKN1A NM_001291549.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1A	NM_001291549.3	c.-142+151T>C		intron_variant	Intron 1 of 3		NP_001278478.1
CDKN1A	NM_001374509.1	c.-50+151T>C		intron_variant	Intron 1 of 3		NP_001361438.1
CDKN1A	NM_001374510.1	c.34+151T>C		intron_variant	Intron 1 of 2		NP_001361439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1A	ENST00000448526.6	c.-38+197T>C		intron_variant	Intron 1 of 3	3		ENSP00000409259.3
CDKN1A	ENST00000615513.4	c.-6+197T>C		intron_variant	Intron 1 of 2	2		ENSP00000482768.1
CDKN1A	ENST00000459970.1	n.43+151T>C		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91101 AN: 151866 Hom.: 28955 Cov.: 31

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.600 AC: 91235 AN: 151986 Hom.: 29024 Cov.: 31 AF XY: 0.600 AC XY: 44604 AN XY: 74284

African (AFR) AF: 0.809 AC: 33520 AN: 41438

American (AMR) AF: 0.650 AC: 9937 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2115 AN: 3464

East Asian (EAS) AF: 0.700 AC: 3623 AN: 5176

South Asian (SAS) AF: 0.492 AC: 2366 AN: 4812

European-Finnish (FIN) AF: 0.447 AC: 4719 AN: 10548

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33111 AN: 67962

Other (OTH) AF: 0.631 AC: 1327 AN: 2104

Alfa AF: 0.532 Hom.: 15323

Bravo AF: 0.630

Asia WGS AF: 0.612 AC: 2128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.55
PhyloP100		-0.73
PromoterAI		-0.035	Neutral

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: rs3829964; hg19: chr6-36644498;