rs2280468

Positions:

• chr15-88838325-C-T

Variant summary

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

The NM_001369268.1(ACAN):​c.71-338C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,020 control chromosomes in the GnomAD database, including 10,472 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 0.36 (10472 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1	c.71-338C>T		intron_variant		ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4	c.71-338C>T		intron_variant		3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53994 AN: 151904 Hom.: 10457 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.356 AC: 54046 AN: 152020 Hom.: 10472 Cov.: 32 AF XY: 0.353 AC XY: 26261 AN XY: 74296

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.340

Alfa AF: 0.320 Hom.: 2399

Bravo AF: 0.367

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.33
DANN	Benign	0.49

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: rs2280468; hg19: chr15-89381556;