15-88838473-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001369268.1(ACAN):c.71-189del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 152,252 control chromosomes in the GnomAD database, including 193 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.038 (193 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41

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 -10 ACMG points.

• BP6: Variant 15-88838473-CT-C is Benign according to our data. Variant chr15-88838473-CT-C is described in ClinVar as [Benign]. Clinvar id is 1264293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1	c.71-189del		intron_variant		ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4	c.71-189del		intron_variant		3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5728 AN: 152134 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0377 AC: 5736 AN: 152252 Hom.: 193 Cov.: 32 AF XY: 0.0380 AC XY: 2827 AN XY: 74448

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.00490 Hom.: 1

Bravo AF: 0.0414

Asia WGS AF: 0.0300 AC: 104 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

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: rs145860113; hg19: chr15-89381704; COSMIC: COSV104419335;