Genetic Variant NM_153000.5:c.243-6G>A (chr18-10471524-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153000.5(APCDD1):c.243-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,613,964 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 25 hom. )

Consequence

APCDD1
NM_153000.5 splice_region, intron

Scores

Splicing: ADA: 0.0003922

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.852

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 18-10471524-G-A is Benign according to our data. Variant chr18-10471524-G-A is described in ClinVar as [Benign]. Clinvar id is 786435.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APCDD1	NM_153000.5 link	c.243-6G>A		splice_region_variant, intron_variant	Intron 2 of 4	ENST00000355285.10	NP_694545.1	Q8J025

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
APCDD1	ENST00000355285.10 link	c.243-6G>A	splice_region_variant, intron_variant	Intron 2 of 4	1	NM_153000.5	ENSP00000347433.4	Q8J025
APCDD1	ENST00000578882.1 link	c.243-6G>A	splice_region_variant, intron_variant	Intron 2 of 4	3		ENSP00000463104.1	J3KTQ6
APCDD1	ENST00000423585.2 link	n.59-13938G>A	intron_variant	Intron 1 of 2	3		ENSP00000404930.2	X6RH63
APCDD1	ENST00000582723.1 link	n.59-6G>A	splice_region_variant, intron_variant	Intron 1 of 2	3		ENSP00000463110.1	J3KTR1

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

278

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.00997

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00410

AC:

1031

AN:

251248

Hom.:

AF XY:

0.00422

AC XY:

573

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.0171

Gnomad SAS exome

AF:

0.0116

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00234

AC:

3415

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1844

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.0154

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.00386

GnomAD4 genome

AF:

0.00182

AC:

277

AN:

152100

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.0160

Gnomad4 SAS

AF:

0.00956

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00165

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.81

CADD

Benign

4.4

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.11

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