15-88835900-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.-7-300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,058 control chromosomes in the GnomAD database, including 36,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (36417 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.513

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=-0.92).
• BP6: Variant 15-88835900-G-A is Benign according to our data. Variant chr15-88835900-G-A is described in ClinVar as [Benign]. Clinvar id is 1286833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1	c.-7-300G>A		intron_variant		ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4	c.-7-300G>A		intron_variant		3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104436 AN: 151940 Hom.: 36396 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.687 AC: 104516 AN: 152058 Hom.: 36417 Cov.: 32 AF XY: 0.687 AC XY: 51075 AN XY: 74316

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.687

Alfa AF: 0.679 Hom.: 4728

Bravo AF: 0.690

Asia WGS AF: 0.566 AC: 1967 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	-0.92
Cadd	Benign	0.86
Dann	Benign	0.66

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: rs938611; hg19: chr15-89379131;