rs4977574

Variant names:

• chr9-22098575-A-G
• rs4977574
• ENST00000428597.6:n.2698+1211A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-22098575-A-G
• chr9-22098575-A-T

Variant summary

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

The ENST00000428597.6(CDKN2B-AS1):​n.2698+1211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,068 control chromosomes in the GnomAD database, including 13,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.40 (13949 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.6 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0800

Genes affected

CDKN2B-AS1 (HGNC:34341): (CDKN2B antisense RNA 1) This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer's disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960). [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2698+1211A>G		intron_variant	Intron 14 of 18
CDKN2B-AS1	NR_047532.2	n.1487+1211A>G		intron_variant	Intron 9 of 13
CDKN2B-AS1	NR_047534.2	n.751+1211A>G		intron_variant	Intron 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.6	n.2698+1211A>G		intron_variant	Intron 14 of 18	1
CDKN2B-AS1	ENST00000577551.5	n.534-13745A>G		intron_variant	Intron 3 of 6	1
CDKN2B-AS1	ENST00000580576.6	n.1487+1211A>G		intron_variant	Intron 9 of 13	1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61532 AN: 151950 Hom.: 13962 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.405 AC: 61534 AN: 152068 Hom.: 13949 Cov.: 32 AF XY: 0.402 AC XY: 29893 AN XY: 74348

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.471

Alfa AF: 0.486 Hom.: 42102

Bravo AF: 0.394

Asia WGS AF: 0.490 AC: 1705 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Other:1

-

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4977574; hg19: chr9-22098574;