chr18-10471287-A-C

Variant names:

• chr18-10471287-A-C
• rs7226906
• NM_153000.5:c.243-243A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153000.5(APCDD1):​c.243-243A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,076 control chromosomes in the GnomAD database, including 3,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3922 hom., cov: 33)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-10471287-A-C is Benign according to our data. Variant chr18-10471287-A-C is described in ClinVar as [Benign]. Clinvar id is 1252435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APCDD1	ENST00000355285.10	c.243-243A>C		intron_variant	Intron 2 of 4	1	NM_153000.5	ENSP00000347433.4
APCDD1	ENST00000578882.1	c.243-243A>C		intron_variant	Intron 2 of 4	3		ENSP00000463104.1
APCDD1	ENST00000423585.2	n.59-14175A>C		intron_variant	Intron 1 of 2	3		ENSP00000404930.2
APCDD1	ENST00000582723.1	n.59-243A>C		intron_variant	Intron 1 of 2	3		ENSP00000463110.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29624 AN: 151958 Hom.: 3914 Cov.: 33

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29679 AN: 152076 Hom.: 3922 Cov.: 33 AF XY: 0.192 AC XY: 14287 AN XY: 74348

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0708 Hom.: 98

Bravo AF: 0.205

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.89
CADD	Benign	0.010
DANN	Benign	0.49

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: rs7226906; hg19: chr18-10471284;