18-10468318-A-G

Position:

• chr18-10468318-A-G

Variant summary

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

The NM_153000.5(APCDD1):​c.59-151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 846,672 control chromosomes in the GnomAD database, including 11,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3037 hom., cov: 34)
  • Exomes 𝑓: 0.15 (8095 hom.)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.238

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=-0.87).
• BP6: Variant 18-10468318-A-G is Benign according to our data. Variant chr18-10468318-A-G is described in ClinVar as [Benign]. Clinvar id is 1273494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APCDD1	NM_153000.5	c.59-151A>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.59-151A>G		intron_variant		1	NM_153000.5	ENSP00000347433.4
APCDD1	ENST00000578882.1	c.59-151A>G		intron_variant		3		ENSP00000463104.1
APCDD1	ENST00000423585.2	n.58+13279A>G		intron_variant		3		ENSP00000404930.2
APCDD1	ENST00000582723.1	n.59-3212A>G		intron_variant		3		ENSP00000463110.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27668 AN: 152078 Hom.: 3029 Cov.: 34

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.146 AC: 101735 AN: 694474 Hom.: 8095 AF XY: 0.147 AC XY: 54254 AN XY: 369732

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.182 AC: 27714 AN: 152198 Hom.: 3037 Cov.: 34 AF XY: 0.178 AC XY: 13257 AN XY: 74428

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.162

Alfa AF: 0.151 Hom.: 378

Bravo AF: 0.188

Asia WGS AF: 0.160 AC: 557 AN: 3478

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	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.34

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: rs3748418; hg19: chr18-10468315;