15-88813601-G-T

Variant names:

• chr15-88813601-G-T
• rs11633371
• NM_001369268.1:c.-8+9792G>T

Variant summary

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

The NM_001369268.1(ACAN):​c.-8+9792G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,012 control chromosomes in the GnomAD database, including 22,496 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 0.54 (22496 hom., cov: 32)
• Consequence: ACAN NM_001369268.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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 (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAN	NM_001369268.1	c.-8+9792G>T		intron_variant	Intron 1 of 18	ENST00000560601.4	NP_001356197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAN	ENST00000560601.4	c.-8+9792G>T		intron_variant	Intron 1 of 18	3	NM_001369268.1	ENSP00000453581.2

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81370 AN: 151894 Hom.: 22457 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.536 AC: 81469 AN: 152012 Hom.: 22496 Cov.: 32 AF XY: 0.547 AC XY: 40634 AN XY: 74318

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.507

Alfa AF: 0.486 Hom.: 37391

Bravo AF: 0.539

Asia WGS AF: 0.680 AC: 2365 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	0.19
DANN	Benign	0.55

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: rs11633371; hg19: chr15-89356832;