Variant chr6-117482879-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001366458.2(DCBLD1):c.98A>G(p.Gln33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,192,396 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

DCBLD1
NM_001366458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.363

Variant links:

Genes affected

DCBLD1 (HGNC:21479): (discoidin, CUB and LCCL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DCBLD1 links:

ENSG00000282218 (HGNC:):

ENSG00000282218 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00461635).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCBLD1	NM_001366458.2 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant	1/15	ENST00000338728.10	NP_001353387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCBLD1	ENST00000338728.10 linkuse as main transcript	c.98A>G	p.Gln33Arg	missense_variant	1/15	5	NM_001366458.2	ENSP00000342422.6		Q8N8Z6-1
ENSG00000282218	ENST00000467125.1 linkuse as main transcript	c.547+83975T>C		intron_variant		2		ENSP00000487717.1		A0A0J9YVX5

Frequencies

GnomAD3 genomes

AF:

0.000186

AC:

AN:

150214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.000223

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.000584

AC:

AN:

13700

Hom.:

AF XY:

0.000747

AC XY:

AN XY:

8030

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.000173

AC:

180

AN:

1042070

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

498626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000578

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.000607

GnomAD4 genome

AF:

0.000186

AC:

AN:

150326

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

AN XY:

73398

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000223

Gnomad4 OTH

AF:

0.000480

Bravo

AF:

0.000178

ExAC

AF:

0.000553

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.98A>G (p.Q33R) alteration is located in exon 1 (coding exon 1) of the DCBLD1 gene. This alteration results from a A to G substitution at nucleotide position 98, causing the glutamine (Q) at amino acid position 33 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.9

DANN

Benign

0.67

DEOGEN2

Benign

0.0050

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.37

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.55

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.21

Sift

Benign

0.53

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.0

B;B

Vest4

0.076

MVP

0.67

MPC

0.29

ClinPred

0.0054

GERP RS

-6.0

Varity_R

0.044

gMVP

0.32

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