Variant 18-10454963-C-G 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 NM_153000.5(APCDD1):c.-19C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 151,982 control chromosomes in the GnomAD database, including 75,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75990 hom., cov: 32)

Exomes 𝑓: 1.0 ( 690023 hom. )

Failed GnomAD Quality Control

Consequence

APCDD1
NM_153000.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.60

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 (BayesDel_noAF=-0.84).

BP6

Variant 18-10454963-C-G is Benign according to our data. Variant chr18-10454963-C-G is described in ClinVar as [Benign]. Clinvar id is 1230499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10454963-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.-19C>G		5_prime_UTR_variant	1/5	ENST00000355285.10	NP_694545.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
APCDD1	ENST00000355285.10 linkuse as main transcript	c.-19C>G	5_prime_UTR_variant	1/5	1	NM_153000.5	ENSP00000347433	P1
APCDD1	ENST00000423585.2 linkuse as main transcript	c.-19C>G	5_prime_UTR_variant, NMD_transcript_variant	1/3	3		ENSP00000404930
APCDD1	ENST00000582723.1 linkuse as main transcript	c.-19C>G	5_prime_UTR_variant, NMD_transcript_variant	1/3	3		ENSP00000463110
APCDD1	ENST00000578882.1 linkuse as main transcript		upstream_gene_variant		3		ENSP00000463104

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

151875

AN:

151876

Hom.:

75937

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

131552

AN:

131552

Hom.:

65776

AF XY:

1.00

AC XY:

71114

AN XY:

71114

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

1.00

AC:

1380049

AN:

1380052

Hom.:

690023

Cov.:

AF XY:

1.00

AC XY:

680822

AN XY:

680824

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

1.00

AC:

151981

AN:

151982

Hom.:

75990

Cov.:

AF XY:

1.00

AC XY:

74272

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

1.00

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

1.00

Hom.:

12894

Bravo

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.6

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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