15-88830608-C-T

Position:

• chr15-88830608-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369268.1(ACAN):​c.-7-5592C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,968 control chromosomes in the GnomAD database, including 29,651 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 0.62 (29651 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1	c.-7-5592C>T		intron_variant		ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4	c.-7-5592C>T		intron_variant		3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94249 AN: 151850 Hom.: 29643 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.621 AC: 94303 AN: 151968 Hom.: 29651 Cov.: 32 AF XY: 0.619 AC XY: 45966 AN XY: 74290

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.643

Alfa AF: 0.631 Hom.: 12250

Bravo AF: 0.618

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.53
DANN	Benign	0.16

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: rs11630178; hg19: chr15-89373839;