15-88836064-G-A

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.-7-136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 631,010 control chromosomes in the GnomAD database, including 114,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26198 hom., cov: 32)
  • Exomes 𝑓: 0.60 (88617 hom.)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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=-0.93).
• BP6: Variant 15-88836064-G-A is Benign according to our data. Variant chr15-88836064-G-A is described in ClinVar as [Benign]. Clinvar id is 1250552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1	c.-7-136G>A		intron_variant		ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4	c.-7-136G>A		intron_variant		3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88019 AN: 151914 Hom.: 26191 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.597 AC: 286155 AN: 478978 Hom.: 88617 AF XY: 0.594 AC XY: 148630 AN XY: 250318

Gnomad4 AFR exome AF: 0.512

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.579 AC: 88073 AN: 152032 Hom.: 26198 Cov.: 32 AF XY: 0.578 AC XY: 42926 AN XY: 74322

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.609

Alfa AF: 0.599 Hom.: 4679

Bravo AF: 0.571

Asia WGS AF: 0.418 AC: 1455 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.092
Dann	Benign	0.48

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: rs938610; hg19: chr15-89379295;