rs10738605

Variant names:

• chr9-22049131-C-A
• rs10738605
• ENST00000428597.7:n.1155C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-22049131-C-A
• chr9-22049131-C-G
• chr9-22049131-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000428597.7(CDKN2B-AS1):​n.1155C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00897 in 152,048 control chromosomes in the GnomAD database, including 19 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 0.0090 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN2B-AS1 ENST00000428597.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.1155C>A		non_coding_transcript_exon_variant	Exon 6 of 19
CDKN2B-AS1	NR_047532.2	n.842C>A		non_coding_transcript_exon_variant	Exon 5 of 14
CDKN2B-AS1	NR_047533.2	n.547C>A		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.7	n.1155C>A		non_coding_transcript_exon_variant	Exon 6 of 19	1
CDKN2B-AS1	ENST00000455933.8	n.516C>A		non_coding_transcript_exon_variant	Exon 3 of 5	1
CDKN2B-AS1	ENST00000577551.5	n.436C>A		non_coding_transcript_exon_variant	Exon 3 of 7	1

Frequencies

GnomAD3 genomes AF: 0.00898 AC: 1364 AN: 151930 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.00431

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00897 AC: 1364 AN: 152048 Hom.: 19 Cov.: 32 AF XY: 0.00946 AC XY: 703 AN XY: 74318

African (AFR) AF: 0.00205 AC: 85 AN: 41476

American (AMR) AF: 0.00255 AC: 39 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.0297 AC: 314 AN: 10562

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 780 AN: 67962

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.0148 Hom.: 655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.72
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10738605; hg19: chr9-22049130;