18-10468456-C-A

Variant names:

• chr18-10468456-C-A
• rs539412
• NM_153000.5:c.59-13C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153000.5(APCDD1):​c.59-13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypotrichosis 1

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000301982 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153000.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APCDD1	NM_153000.5	MANE Select	c.59-13C>A		intron	N/A	NP_694545.1	Q8J025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APCDD1	ENST00000355285.10	TSL:1 MANE Select	c.59-13C>A		intron	N/A	ENSP00000347433.4	Q8J025
	APCDD1	ENST00000578882.1	TSL:3	c.59-13C>A		intron	N/A	ENSP00000463104.1	J3KTQ6
	APCDD1	ENST00000423585.2	TSL:3	n.58+13417C>A		intron	N/A	ENSP00000404930.2	X6RH63

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461764 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.61
DANN	Benign	0.31
PhyloP100		-0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs539412; hg19: chr18-10468453;