18-10455080-A-G

Position:

• chr18-10455080-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000355285.10(APCDD1):​c.58+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,546,900 control chromosomes in the GnomAD database, including 226,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (27047 hom., cov: 34)
  • Exomes 𝑓: 0.53 (199717 hom.)
• Consequence: APCDD1 ENST00000355285.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.49

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 18-10455080-A-G is Benign according to our data. Variant chr18-10455080-A-G is described in ClinVar as [Benign]. Clinvar id is 1270753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APCDD1	NM_153000.5	c.58+41A>G		intron_variant		ENST00000355285.10	NP_694545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APCDD1	ENST00000355285.10	c.58+41A>G		intron_variant		1	NM_153000.5	ENSP00000347433.4
APCDD1	ENST00000578882.1	c.58+41A>G		intron_variant		3		ENSP00000463104.1
APCDD1	ENST00000423585.2	n.58+41A>G		intron_variant		3		ENSP00000404930.2
APCDD1	ENST00000582723.1	n.58+41A>G		intron_variant		3		ENSP00000463110.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88435 AN: 151842 Hom.: 27000 Cov.: 34

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.577

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.569

GnomAD3 exomes AF: 0.486 AC: 69945 AN: 143926 Hom.: 17612 AF XY: 0.486 AC XY: 37769 AN XY: 77704

Gnomad AFR exome AF: 0.791

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.463

Gnomad SAS exome AF: 0.451

Gnomad FIN exome AF: 0.423

Gnomad NFE exome AF: 0.531

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.531 AC: 740643 AN: 1394948 Hom.: 199717 Cov.: 56 AF XY: 0.527 AC XY: 362983 AN XY: 688248

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.583 AC: 88537 AN: 151952 Hom.: 27047 Cov.: 34 AF XY: 0.572 AC XY: 42513 AN XY: 74278

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.566

Alfa AF: 0.533 Hom.: 3947

Bravo AF: 0.595

Asia WGS AF: 0.468 AC: 1627 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.14

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

Other links and lift over

dbSNP: rs28379930; hg19: chr18-10455077; COSMIC: COSV62373461;