rs938611

Variant names:

• chr15-88835900-G-A
• rs938611
• NM_001369268.1:c.-7-300G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-88835900-G-A
• chr15-88835900-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ACAN Gene-Disease associations (from GenCC):

• ACAN-related short stature spectrum

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• osteochondritis dissecans

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
• short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• spondyloepiphyseal dysplasia, Kimberley type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia, aggrecan type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• short stature-advanced bone age-early-onset osteoarthritis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369268.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAN	NM_001369268.1	MANE Select	c.-7-300G>A		intron	N/A	NP_001356197.1	P16112-4
	ACAN	NM_001411097.1		c.-7-300G>A		intron	N/A	NP_001398026.1	A0A5K1VW97
	ACAN	NM_013227.4		c.-7-300G>A		intron	N/A	NP_037359.3	P16112-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAN	ENST00000560601.4	TSL:3 MANE Select	c.-7-300G>A		intron	N/A	ENSP00000453581.2	P16112-4
	ACAN	ENST00000558207.5	TSL:1	c.-7-300G>A		intron	N/A	ENSP00000453003.1	Q6PID9
	ACAN	ENST00000439576.7	TSL:5	c.-7-300G>A		intron	N/A	ENSP00000387356.2	P16112-1

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

African (AFR) AF: 0.787 AC: 32671 AN: 41488

American (AMR) AF: 0.655 AC: 10004 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2093 AN: 5172

South Asian (SAS) AF: 0.574 AC: 2764 AN: 4814

European-Finnish (FIN) AF: 0.725 AC: 7655 AN: 10562

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44771 AN: 67960

Other (OTH) AF: 0.687 AC: 1447 AN: 2106

Alfa AF: 0.683 Hom.: 4966

Bravo AF: 0.690

Asia WGS AF: 0.566 AC: 1967 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.66
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs938611; hg19: chr15-89379131;