Variant 18-10471735-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000355285.10(APCDD1):c.448G>A(p.Val150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,984 control chromosomes in the GnomAD database, including 12,427 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.091 ( 817 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11610 hom. )

Consequence

APCDD1
ENST00000355285.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

APCDD1 (HGNC:15718): (APC down-regulated 1) This locus encodes an inhibitor of the Wnt signaling pathway. Mutations at this locus have been associated with hereditary hypotrichosis simplex. Increased expression of this gene may also be associated with colorectal carcinogenesis.[provided by RefSeq, Sep 2010]

APCDD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018335283).

BP6

Variant 18-10471735-G-A is Benign according to our data. Variant chr18-10471735-G-A is described in ClinVar as [Benign]. Clinvar id is 1286582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10471735-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APCDD1	NM_153000.5 linkuse as main transcript	c.448G>A	p.Val150Ile	missense_variant	3/5	ENST00000355285.10	NP_694545.1	Q8J025

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APCDD1	ENST00000355285.10 linkuse as main transcript	c.448G>A	p.Val150Ile	missense_variant	3/5	1	NM_153000.5	ENSP00000347433.4		Q8J025

Frequencies

GnomAD3 genomes

AF:

0.0914

AC:

13916

AN:

152176

Hom.:

814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.0888

Gnomad ASJ

AF:

0.0876

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.0922

GnomAD3 exomes

AF:

0.116

AC:

29019

AN:

251168

Hom.:

1903

AF XY:

0.122

AC XY:

16576

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.0760

Gnomad ASJ exome

AF:

0.0914

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.123

AC:

179977

AN:

1461690

Hom.:

11610

Cov.:

AF XY:

0.125

AC XY:

90998

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.0797

Gnomad4 ASJ exome

AF:

0.0892

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.0914

AC:

13925

AN:

152294

Hom.:

817

Cov.:

AF XY:

0.0913

AC XY:

6799

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0237

Gnomad4 AMR

AF:

0.0895

Gnomad4 ASJ

AF:

0.0876

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.0912

Alfa

AF:

0.111

Hom.:

1743

Bravo

AF:

0.0859

TwinsUK

AF:

0.123

AC:

456

ALSPAC

AF:

0.134

AC:

518

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.120

AC:

1034

ExAC

AF:

0.117

AC:

14239

Asia WGS

AF:

0.115

AC:

401

AN:

3478

EpiCase

AF:

0.128

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-0.097

Eigen_PC

Benign

-0.056

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.57

P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.78

N;.

REVEL

Benign

0.018

Sift

Benign

0.18

T;.

Sift4G

Benign

0.084

T;T

Polyphen

0.39

B;.

Vest4

0.097

MPC

0.24

ClinPred

0.0058

GERP RS

4.4

Varity_R

0.046

gMVP

0.18

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