rs8042988

Positions:

• chr15-88869048-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.7060+719A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,992 control chromosomes in the GnomAD database, including 15,427 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 0.43 (15427 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAN	NM_001369268.1	c.7060+719A>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.7060+719A>G		intron_variant		3	NM_001369268.1	ENSP00000453581.2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64717 AN: 151874 Hom.: 15379 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.426 AC: 64819 AN: 151992 Hom.: 15427 Cov.: 32 AF XY: 0.423 AC XY: 31452 AN XY: 74276

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.405

Alfa AF: 0.346 Hom.: 15882

Bravo AF: 0.432

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.51

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: rs8042988; hg19: chr15-89412279;