rs9630453

chr15-88860691-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001369268.1(ACAN):c.6946+252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,204 control chromosomes in the GnomAD database, including 8,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (8937 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.388

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-88860691-A-G is Benign according to our data. Variant chr15-88860691-A-G is described in ClinVar as [Benign]. Clinvar id is 1293765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1	c.6946+252A>G		intron_variant		ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4	c.6946+252A>G		intron_variant		3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37158 AN: 152086 Hom.: 8893 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.245 AC: 37252 AN: 152204 Hom.: 8937 Cov.: 32 AF XY: 0.242 AC XY: 18028 AN XY: 74422

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0648

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.0554

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.206

Alfa AF: 0.134 Hom.: 1682

Bravo AF: 0.265

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9630453; hg19: chr15-89403922;