rs28484275

Variant names:

• chr18-10455136-C-T
• rs28484275
• NM_153000.5:c.58+97C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-10455136-C-T
• chr18-10455136-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153000.5(APCDD1):​c.58+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,518,442 control chromosomes in the GnomAD database, including 223,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26987 hom., cov: 33)
  • Exomes 𝑓: 0.53 (196082 hom.)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.658
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae)
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000301982 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-10455136-C-T is Benign according to our data. Variant chr18-10455136-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

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.58+97C>T		intron	N/A	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.58+97C>T		intron	N/A	ENSP00000347433.4	Q8J025
	APCDD1	ENST00000578882.1	TSL:3	c.58+97C>T		intron	N/A	ENSP00000463104.1	J3KTQ6
	ENSG00000301982	ENST00000783193.1		n.12G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88288 AN: 151820 Hom.: 26938 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.577

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.532 AC: 727159 AN: 1366508 Hom.: 196082 AF XY: 0.529 AC XY: 356206 AN XY: 673694

African (AFR) AF: 0.792 AC: 23504 AN: 29690

American (AMR) AF: 0.427 AC: 14175 AN: 33172

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 10621 AN: 23794

East Asian (EAS) AF: 0.447 AC: 15259 AN: 34144

South Asian (SAS) AF: 0.450 AC: 34341 AN: 76242

European-Finnish (FIN) AF: 0.438 AC: 19471 AN: 44464

Middle Eastern (MID) AF: 0.572 AC: 2327 AN: 4070

European-Non Finnish (NFE) AF: 0.542 AC: 577322 AN: 1064522

Other (OTH) AF: 0.534 AC: 30139 AN: 56410

GnomAD4 genome AF: 0.582 AC: 88394 AN: 151934 Hom.: 26987 Cov.: 33 AF XY: 0.571 AC XY: 42437 AN XY: 74270

African (AFR) AF: 0.776 AC: 32206 AN: 41492

American (AMR) AF: 0.495 AC: 7567 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3466

East Asian (EAS) AF: 0.450 AC: 2285 AN: 5082

South Asian (SAS) AF: 0.460 AC: 2216 AN: 4820

European-Finnish (FIN) AF: 0.424 AC: 4481 AN: 10574

Middle Eastern (MID) AF: 0.572 AC: 166 AN: 290

European-Non Finnish (NFE) AF: 0.534 AC: 36237 AN: 67886

Other (OTH) AF: 0.567 AC: 1200 AN: 2116

Alfa AF: 0.385 Hom.: 906

Bravo AF: 0.594

Asia WGS AF: 0.455 AC: 1583 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.89
PhyloP100		-0.66
PromoterAI		-0.39	Neutral
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: rs28484275; hg19: chr18-10455133; COSMIC: COSV62373465;