Variant 18-10468456-C-T 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.59-13C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,613,496 control chromosomes in the GnomAD database, including 108,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9784 hom., cov: 33)

Exomes 𝑓: 0.36 ( 98889 hom. )

Consequence

APCDD1
NM_153000.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0980

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=-0.92).

BP6

Variant 18-10468456-C-T is Benign according to our data. Variant chr18-10468456-C-T is described in ClinVar as [Benign]. Clinvar id is 1282275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10468456-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 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.59-13C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000355285.10	NP_694545.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
APCDD1	ENST00000355285.10 linkuse as main transcript	c.59-13C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_153000.5	ENSP00000347433	P1
APCDD1	ENST00000578882.1 linkuse as main transcript	c.59-13C>T	splice_polypyrimidine_tract_variant, intron_variant	3		ENSP00000463104
APCDD1	ENST00000423585.2 linkuse as main transcript	c.58+13417C>T	intron_variant, NMD_transcript_variant	3		ENSP00000404930
APCDD1	ENST00000582723.1 linkuse as main transcript	c.59-3074C>T	intron_variant, NMD_transcript_variant	3		ENSP00000463110

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53572

AN:

151982

Hom.:

9767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.384

AC:

96468

AN:

251380

Hom.:

19745

AF XY:

0.380

AC XY:

51621

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.338

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.362

AC:

528901

AN:

1461396

Hom.:

98889

Cov.:

AF XY:

0.362

AC XY:

262843

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.476

Gnomad4 ASJ exome

AF:

0.341

Gnomad4 EAS exome

AF:

0.673

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.349

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.353

AC:

53639

AN:

152100

Hom.:

9784

Cov.:

AF XY:

0.358

AC XY:

26583

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.450

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.345

Hom.:

4048

Bravo

AF:

0.360

Asia WGS

AF:

0.452

AC:

1572

AN:

3478

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.78

DANN

Benign

0.22

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