rs28769876

Variant names:

• chr18-10454963-C-A
• rs28769876
• NM_153000.5:c.-19C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-10454963-C-A
• chr18-10454963-C-G
• chr18-10454963-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153000.5(APCDD1):​c.-19C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APCDD1 NM_153000.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 9 publications found

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]

APCDD1 Gene-Disease associations (from GenCC):

• hypotrichosis 1

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000301982 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153000.5. 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
	APCDD1	NM_153000.5	MANE Select	c.-19C>A		5_prime_UTR	Exon 1 of 5	NP_694545.1	Q8J025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APCDD1	ENST00000355285.10	TSL:1 MANE Select	c.-19C>A		5_prime_UTR	Exon 1 of 5	ENSP00000347433.4	Q8J025
	APCDD1	ENST00000423585.2	TSL:3	n.-19C>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000404930.2	X6RH63
	APCDD1	ENST00000582723.1	TSL:3	n.-19C>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000463110.1	J3KTR1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1380052 Hom.: 0 Cov.: 64 AF XY: 0.00 AC XY: 0 AN XY: 680824

African (AFR) AF: 0.00 AC: 0 AN: 28802

American (AMR) AF: 0.00 AC: 0 AN: 34464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24440

East Asian (EAS) AF: 0.00 AC: 0 AN: 33336

South Asian (SAS) AF: 0.00 AC: 0 AN: 77006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072052

Other (OTH) AF: 0.00 AC: 0 AN: 57142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.70
PhyloP100		-2.6
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

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: rs28769876; hg19: chr18-10454960;