Variant 15-88856926-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001369268.1(ACAN):c.4341G>T(p.Glu1447Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,568,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

ACAN
NM_001369268.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.07

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040175796).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAN	NM_001369268.1 linkuse as main transcript	c.4341G>T	p.Glu1447Asp	missense_variant	12/19	ENST00000560601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAN	ENST00000560601.4 linkuse as main transcript	c.4341G>T	p.Glu1447Asp	missense_variant	12/19	3	NM_001369268.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000153

AC:

AN:

131112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000334

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1437260

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

715376

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000338

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000153

AC:

AN:

131112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64586

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000334

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.0010

DANN

Benign

0.22

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.29

T;T;T;T;T;.

M_CAP

Benign

0.079

MetaRNN

Benign

0.040

T;T;T;T;T;T

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.51

Vest4

0.029, 0.032, 0.036, 0.037, 0.022

MutPred

0.27

Loss of phosphorylation at S1449 (P = 0.3149);Loss of phosphorylation at S1449 (P = 0.3149);.;Loss of phosphorylation at S1449 (P = 0.3149);Loss of phosphorylation at S1449 (P = 0.3149);Loss of phosphorylation at S1449 (P = 0.3149);

MVP

0.14

MPC

0.18

ClinPred

0.038

GERP RS

-5.3

Varity_R

0.032

gMVP

0.055

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over