rs8041863

Positions:

• chr15-88816458-T-A
• chr15-88816458-T-C
• chr15-88816458-T-G

Variant summary

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

The NM_001369268.1(ACAN):​c.-8+12649T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,034 control chromosomes in the GnomAD database, including 22,668 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 0.54 (22668 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1	c.-8+12649T>A		intron_variant		ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4	c.-8+12649T>A		intron_variant		3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81698 AN: 151916 Hom.: 22627 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.538 AC: 81795 AN: 152034 Hom.: 22668 Cov.: 32 AF XY: 0.549 AC XY: 40814 AN XY: 74330

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.510

Alfa AF: 0.476 Hom.: 9280

Bravo AF: 0.539

Asia WGS AF: 0.703 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.41
DANN	Benign	0.46

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: rs8041863; hg19: chr15-89359689;