20-58511618-G-A

Variant names:

• chr20-58511618-G-A
• rs2208087
• NM_153360.3:c.49+3041C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153360.3(APCDD1L):​c.49+3041C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,112 control chromosomes in the GnomAD database, including 19,170 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 0.47 (19170 hom., cov: 33)
• Consequence: APCDD1L NM_153360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 4 publications found

Genes affected

APCDD1L (HGNC:26892): (APC down-regulated 1 like) Predicted to enable Wnt-protein binding activity. Predicted to be involved in negative regulation of Wnt signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153360.3. 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
	APCDD1L	NM_153360.3	MANE Select	c.49+3041C>T		intron	N/A	NP_699191.1	Q8NCL9
	APCDD1L	NM_001304787.2		c.82+2199C>T		intron	N/A	NP_001291716.1
	APCDD1L	NR_130908.2		n.741+3041C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APCDD1L	ENST00000371149.8	TSL:1 MANE Select	c.49+3041C>T		intron	N/A	ENSP00000360191.3	Q8NCL9
	APCDD1L	ENST00000853970.1		c.49+3041C>T		intron	N/A	ENSP00000524029.1
	APCDD1L	ENST00000425773.1	TSL:5	c.82+2199C>T		intron	N/A	ENSP00000396856.1	A2A2P3

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72013 AN: 151994 Hom.: 19149 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.474 AC: 72066 AN: 152112 Hom.: 19170 Cov.: 33 AF XY: 0.477 AC XY: 35507 AN XY: 74366

African (AFR) AF: 0.226 AC: 9391 AN: 41506

American (AMR) AF: 0.595 AC: 9093 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1698 AN: 3468

East Asian (EAS) AF: 0.355 AC: 1836 AN: 5170

South Asian (SAS) AF: 0.457 AC: 2207 AN: 4826

European-Finnish (FIN) AF: 0.659 AC: 6962 AN: 10572

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39103 AN: 67964

Other (OTH) AF: 0.475 AC: 1004 AN: 2114

Alfa AF: 0.476 Hom.: 3828

Bravo AF: 0.459

Asia WGS AF: 0.423 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		-0.064
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2208087; hg19: chr20-57086674;