rs547668

Positions:

• chr18-10476824-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153000.5(APCDD1):​c.774+4763G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,224 control chromosomes in the GnomAD database, including 5,970 homozygotes. 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: 𝑓 0.24 (5968 hom., cov: 33)
  • Exomes 𝑓: 0.28 (2 hom.)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APCDD1	NM_153000.5	c.774+4763G>T		intron_variant		ENST00000355285.10	NP_694545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APCDD1	ENST00000355285.10	c.774+4763G>T		intron_variant		1	NM_153000.5	ENSP00000347433.4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36549 AN: 152088 Hom.: 5961 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.278 AC: 5 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.357 AC XY: 5 AN XY: 14

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.240 AC: 36592 AN: 152206 Hom.: 5968 Cov.: 33 AF XY: 0.236 AC XY: 17584 AN XY: 74448

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.203

Alfa AF: 0.168 Hom.: 3038

Bravo AF: 0.255

Asia WGS AF: 0.169 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.58

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: rs547668; hg19: chr18-10476821;