Variant rs3746373 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020882.4(COL20A1):c.498C>A(p.Ala166=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00541 in 1,610,740 control chromosomes in the GnomAD database, including 287 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0079 ( 35 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 252 hom. )

Consequence

COL20A1
NM_020882.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001391

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.101

Variant links:

Genes affected

COL20A1 (HGNC:14670): (collagen type XX alpha 1 chain) Predicted to be located in endoplasmic reticulum lumen and extracellular region. Predicted to be part of collagen trimer. Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

COL20A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL20A1	NM_020882.4 linkuse as main transcript	c.498C>A	p.Ala166=	splice_region_variant, synonymous_variant	6/36	ENST00000358894.11	NP_065933.2
COL20A1	XM_011528937.2 linkuse as main transcript	c.498C>A	p.Ala166=	splice_region_variant, synonymous_variant	6/36		XP_011527239.1
COL20A1	XM_011528938.2 linkuse as main transcript	c.498C>A	p.Ala166=	splice_region_variant, synonymous_variant	6/36		XP_011527240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL20A1	ENST00000358894.11 linkuse as main transcript	c.498C>A	p.Ala166=	splice_region_variant, synonymous_variant	6/36	1	NM_020882.4	ENSP00000351767	P2	Q9P218-1
COL20A1	ENST00000479501.5 linkuse as main transcript	n.560C>A		splice_region_variant, non_coding_transcript_exon_variant	6/36	1
COL20A1	ENST00000422202.5 linkuse as main transcript	c.519C>A	p.Thr173=	splice_region_variant, synonymous_variant	5/35	5		ENSP00000414753	A2	Q9P218-2

Frequencies

GnomAD3 genomes

AF:

0.00792

AC:

1206

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00997

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.0182

AC:

4448

AN:

244806

Hom.:

186

AF XY:

0.0151

AC XY:

2014

AN XY:

133618

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.0590

Gnomad ASJ exome

AF:

0.00224

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.00203

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.000906

Gnomad OTH exome

AF:

0.0115

GnomAD4 exome

AF:

0.00516

AC:

7522

AN:

1458420

Hom.:

252

Cov.:

AF XY:

0.00477

AC XY:

3463

AN XY:

725542

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.0556

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.0789

Gnomad4 SAS exome

AF:

0.00222

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.000494

Gnomad4 OTH exome

AF:

0.00889

GnomAD4 genome

AF:

0.00788

AC:

1200

AN:

152320

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

663

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.0267

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00997

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.0102

EpiCase

AF:

0.000218

EpiControl

AF:

0.000297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.032

SpliceAI score (max)

0.98

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.98

Position offset: 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