chr18-10468330-A-G

Variant names:

• chr18-10468330-A-G
• rs3748417
• NM_153000.5:c.59-139A>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.59-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 900,672 control chromosomes in the GnomAD database, including 11,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2853 hom., cov: 34)
  • Exomes 𝑓: 0.15 (8616 hom.)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.658

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=-0.88).
• BP6: Variant 18-10468330-A-G is Benign according to our data. Variant chr18-10468330-A-G is described in ClinVar as [Benign]. Clinvar id is 1239646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APCDD1	NM_153000.5	c.59-139A>G		intron_variant	Intron 1 of 4	ENST00000355285.10	NP_694545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APCDD1	ENST00000355285.10	c.59-139A>G		intron_variant	Intron 1 of 4	1	NM_153000.5	ENSP00000347433.4
APCDD1	ENST00000578882.1	c.59-139A>G		intron_variant	Intron 1 of 4	3		ENSP00000463104.1
APCDD1	ENST00000423585.2	n.58+13291A>G		intron_variant	Intron 1 of 2	3		ENSP00000404930.2
APCDD1	ENST00000582723.1	n.59-3200A>G		intron_variant	Intron 1 of 2	3		ENSP00000463110.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27025 AN: 152030 Hom.: 2844 Cov.: 34

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.146 AC: 109143 AN: 748522 Hom.: 8616 AF XY: 0.146 AC XY: 58175 AN XY: 397512

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.178 AC: 27072 AN: 152150 Hom.: 2853 Cov.: 34 AF XY: 0.174 AC XY: 12961 AN XY: 74402

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.160

Alfa AF: 0.155 Hom.: 256

Bravo AF: 0.184

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

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	-0.88
CADD	Benign	0.31
DANN	Benign	0.27

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: rs3748417; hg19: chr18-10468327;