rs2280470

Positions:

• chr15-88852395-A-G

Variant summary

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

The NM_001369268.1(ACAN):​c.2266+362A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,032 control chromosomes in the GnomAD database, including 35,646 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 0.67 (35646 hom., cov: 31)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

Genes affected

ACAN (HGNC:319): (aggrecan) This gene is a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage. Mutations in this gene may be involved in skeletal dysplasia and spinal degeneration. Multiple alternatively spliced transcript variants that encode different protein isoforms have been observed in this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAN	NM_001369268.1	c.2266+362A>G		intron_variant		ENST00000560601.4	NP_001356197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAN	ENST00000560601.4	c.2266+362A>G		intron_variant		3	NM_001369268.1	ENSP00000453581	P1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102437 AN: 151914 Hom.: 35629 Cov.: 31

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.674 AC: 102501 AN: 152032 Hom.: 35646 Cov.: 31 AF XY: 0.664 AC XY: 49333 AN XY: 74312

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.672

Alfa AF: 0.673 Hom.: 8228

Bravo AF: 0.669

Asia WGS AF: 0.486 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.79
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs2280470; hg19: chr15-89395626;