Genetic Variant APCDD1:c.58+97C>T (chr18-10455136-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153000.5(APCDD1):c.58+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,518,442 control chromosomes in the GnomAD database, including 223,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26987 hom., cov: 33)

Exomes 𝑓: 0.53 ( 196082 hom. )

Consequence

APCDD1
NM_153000.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.658

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 18-10455136-C-T is Benign according to our data. Variant chr18-10455136-C-T is described in ClinVar as [Benign]. Clinvar id is 1221986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APCDD1	NM_153000.5 link	c.58+97C>T		intron_variant	Intron 1 of 4	ENST00000355285.10	NP_694545.1	Q8J025

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
APCDD1	ENST00000355285.10 link	c.58+97C>T	intron_variant	Intron 1 of 4	1	NM_153000.5	ENSP00000347433.4	Q8J025
APCDD1	ENST00000578882.1 link	c.58+97C>T	intron_variant	Intron 1 of 4	3		ENSP00000463104.1	J3KTQ6
APCDD1	ENST00000423585.2 link	n.58+97C>T	intron_variant	Intron 1 of 2	3		ENSP00000404930.2	X6RH63
APCDD1	ENST00000582723.1 link	n.58+97C>T	intron_variant	Intron 1 of 2	3		ENSP00000463110.1	J3KTR1

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88288

AN:

151820

Hom.:

26938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.776

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.449

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.577

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.570

GnomAD4 exome

AF:

0.532

AC:

727159

AN:

1366508

Hom.:

196082

AF XY:

0.529

AC XY:

356206

AN XY:

673694

show subpopulations

Gnomad4 AFR exome

AF:

0.792

AC:

23504

AN:

29690

Gnomad4 AMR exome

AF:

0.427

AC:

14175

AN:

33172

Gnomad4 ASJ exome

AF:

0.446

AC:

10621

AN:

23794

Gnomad4 EAS exome

AF:

0.447

AC:

15259

AN:

34144

Gnomad4 SAS exome

AF:

0.450

AC:

34341

AN:

76242

Gnomad4 FIN exome

AF:

0.438

AC:

19471

AN:

44464

Gnomad4 NFE exome

AF:

0.542

AC:

577322

AN:

1064522

Gnomad4 Remaining exome

AF:

0.534

AC:

30139

AN:

56410

Heterozygous variant carriers

15619

31239

46858

62478

78097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

16712

33424

50136

66848

83560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.582

AC:

88394

AN:

151934

Hom.:

26987

Cov.:

AF XY:

0.571

AC XY:

42437

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.776

AC:

0.776198

AN:

0.776198

Gnomad4 AMR

AF:

0.495

AC:

0.494575

AN:

0.494575

Gnomad4 ASJ

AF:

0.445

AC:

0.444893

AN:

0.444893

Gnomad4 EAS

AF:

0.450

AC:

0.449626

AN:

0.449626

Gnomad4 SAS

AF:

0.460

AC:

0.459751

AN:

0.459751

Gnomad4 FIN

AF:

0.424

AC:

0.423775

AN:

0.423775

Gnomad4 NFE

AF:

0.534

AC:

0.533792

AN:

0.533792

Gnomad4 OTH

AF:

0.567

AC:

0.567108

AN:

0.567108

Heterozygous variant carriers

1786

3572

5358

7144

8930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.385

Hom.:

906

Bravo

AF:

0.594

Asia WGS

AF:

0.455

AC:

1583

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.8

DANN

Benign

0.89

Mutation Taster

=100/0

polymorphism (auto)

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