18-10468456-C-T

Variant names:

• chr18-10468456-C-T
• rs539412
• NM_153000.5:c.59-13C>T

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.59-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,613,496 control chromosomes in the GnomAD database, including 108,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9784 hom., cov: 33)
  • Exomes 𝑓: 0.36 (98889 hom.)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0980
• Publications: 8 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=-0.92).
• BP6: Variant 18-10468456-C-T is Benign according to our data. Variant chr18-10468456-C-T is described in ClinVar as Benign. ClinVar VariationId is 1282275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 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.59-13C>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.59-13C>T		intron	N/A	ENSP00000347433.4	Q8J025
	APCDD1	ENST00000578882.1	TSL:3	c.59-13C>T		intron	N/A	ENSP00000463104.1	J3KTQ6
	APCDD1	ENST00000423585.2	TSL:3	n.58+13417C>T		intron	N/A	ENSP00000404930.2	X6RH63

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53572 AN: 151982 Hom.: 9767 Cov.: 33

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.384 AC: 96468 AN: 251380 AF XY: 0.380

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.338

Gnomad EAS exome AF: 0.648

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.362 AC: 528901 AN: 1461396 Hom.: 98889 Cov.: 40 AF XY: 0.362 AC XY: 262843 AN XY: 727034

African (AFR) AF: 0.296 AC: 9902 AN: 33464

American (AMR) AF: 0.476 AC: 21291 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8912 AN: 26134

East Asian (EAS) AF: 0.673 AC: 26731 AN: 39694

South Asian (SAS) AF: 0.371 AC: 31986 AN: 86230

European-Finnish (FIN) AF: 0.338 AC: 18028 AN: 53414

Middle Eastern (MID) AF: 0.381 AC: 2176 AN: 5704

European-Non Finnish (NFE) AF: 0.349 AC: 387690 AN: 1111672

Other (OTH) AF: 0.368 AC: 22185 AN: 60362

GnomAD4 genome AF: 0.353 AC: 53639 AN: 152100 Hom.: 9784 Cov.: 33 AF XY: 0.358 AC XY: 26583 AN XY: 74336

African (AFR) AF: 0.301 AC: 12468 AN: 41488

American (AMR) AF: 0.450 AC: 6873 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3288 AN: 5186

South Asian (SAS) AF: 0.387 AC: 1867 AN: 4828

European-Finnish (FIN) AF: 0.327 AC: 3451 AN: 10558

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23227 AN: 67964

Other (OTH) AF: 0.374 AC: 789 AN: 2112

Alfa AF: 0.344 Hom.: 7040

Bravo AF: 0.360

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.22
PhyloP100		-0.098
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: rs539412; hg19: chr18-10468453; COSMIC: COSV62372243; COSMIC: COSV62372243;