Variant 6-56124072-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_030820.4(COL21A1):c.1748C>G(p.Pro583Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0138 in 1,515,634 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P583S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.010 ( 17 hom., cov: 32)

Exomes 𝑓: 0.014 ( 153 hom. )

Consequence

COL21A1
NM_030820.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

COL21A1 (HGNC:17025): (collagen type XXI alpha 1 chain) This gene encodes the alpha chain of type XXI collagen, a member of the FACIT (fibril-associated collagens with interrupted helices) collagen family. Type XXI collagen is localized to tissues containing type I collagen and maintains the integrity of the extracellular matrix. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

COL21A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017270327).

BP6

Variant 6-56124072-G-C is Benign according to our data. Variant chr6-56124072-G-C is described in ClinVar as [Benign]. Clinvar id is 771715.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0103 (1538/148866) while in subpopulation NFE AF= 0.0171 (1152/67346). AF 95% confidence interval is 0.0163. There are 17 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL21A1	NM_030820.4 linkuse as main transcript	c.1748C>G	p.Pro583Arg	missense_variant	16/30	ENST00000244728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL21A1	ENST00000244728.10 linkuse as main transcript	c.1748C>G	p.Pro583Arg	missense_variant	16/30	1	NM_030820.4	A1	Q96P44-1
COL21A1	ENST00000370819.5 linkuse as main transcript	c.1739C>G	p.Pro580Arg	missense_variant	15/29	1		P4	Q96P44-3
COL21A1	ENST00000488912.5 linkuse as main transcript	c.140C>G	p.Pro47Arg	missense_variant, NMD_transcript_variant	3/18	1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1540

AN:

148786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00274

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00607

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00189

Gnomad FIN

AF:

0.00248

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0141

GnomAD3 exomes

AF:

0.00882

AC:

1168

AN:

132470

Hom.:

AF XY:

0.00863

AC XY:

602

AN XY:

69748

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.00859

Gnomad ASJ exome

AF:

0.00691

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00299

Gnomad FIN exome

AF:

0.00253

Gnomad NFE exome

AF:

0.0151

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.0142

AC:

19402

AN:

1366768

Hom.:

153

Cov.:

AF XY:

0.0141

AC XY:

9464

AN XY:

673458

show subpopulations

Gnomad4 AFR exome

AF:

0.00228

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.00749

Gnomad4 EAS exome

AF:

0.0000570

Gnomad4 SAS exome

AF:

0.00279

Gnomad4 FIN exome

AF:

0.00335

Gnomad4 NFE exome

AF:

0.0165

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0103

AC:

1538

AN:

148866

Hom.:

Cov.:

AF XY:

0.00986

AC XY:

715

AN XY:

72490

show subpopulations

Gnomad4 AFR

AF:

0.00273

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00607

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00190

Gnomad4 FIN

AF:

0.00248

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0140

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0104

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0150

AC:

ESP6500AA

AF:

0.00276

AC:

ESP6500EA

AF:

0.00943

AC:

ExAC

AF:

0.00367

AC:

282

Asia WGS

AF:

0.00116

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 17, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

D;D;D

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.0

N;N;.

REVEL

Pathogenic

0.73

Sift

Benign

0.62

T;T;.

Sift4G

Benign

0.10

T;D;T

Polyphen

0.99

D;.;.

Vest4

0.44

MVP

0.75

MPC

0.099

ClinPred

0.024

GERP RS

4.4

Varity_R

0.10

gMVP

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over