18-10468318-A-G

Variant names:

• chr18-10468318-A-G
• rs3748418
• NM_153000.5:c.59-151A>G

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.59-151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 846,672 control chromosomes in the GnomAD database, including 11,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3037 hom., cov: 34)
  • Exomes 𝑓: 0.15 (8095 hom.)
• Consequence: APCDD1 NM_153000.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.238
• Publications: 0 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 18-10468318-A-G is Benign according to our data. Variant chr18-10468318-A-G is described in ClinVar as Benign. ClinVar VariationId is 1273494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 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.59-151A>G		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.59-151A>G		intron	N/A	ENSP00000347433.4	Q8J025
	APCDD1	ENST00000578882.1	TSL:3	c.59-151A>G		intron	N/A	ENSP00000463104.1	J3KTQ6
	APCDD1	ENST00000423585.2	TSL:3	n.58+13279A>G		intron	N/A	ENSP00000404930.2	X6RH63

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27668 AN: 152078 Hom.: 3029 Cov.: 34

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.146 AC: 101735 AN: 694474 Hom.: 8095 AF XY: 0.147 AC XY: 54254 AN XY: 369732

African (AFR) AF: 0.309 AC: 5896 AN: 19076

American (AMR) AF: 0.106 AC: 4390 AN: 41302

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2173 AN: 19392

East Asian (EAS) AF: 0.148 AC: 5332 AN: 36092

South Asian (SAS) AF: 0.169 AC: 10929 AN: 64728

European-Finnish (FIN) AF: 0.112 AC: 4621 AN: 41236

Middle Eastern (MID) AF: 0.192 AC: 505 AN: 2624

European-Non Finnish (NFE) AF: 0.144 AC: 62608 AN: 434932

Other (OTH) AF: 0.150 AC: 5281 AN: 35092

GnomAD4 genome AF: 0.182 AC: 27714 AN: 152198 Hom.: 3037 Cov.: 34 AF XY: 0.178 AC XY: 13257 AN XY: 74428

African (AFR) AF: 0.303 AC: 12580 AN: 41464

American (AMR) AF: 0.130 AC: 1993 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3472

East Asian (EAS) AF: 0.162 AC: 838 AN: 5186

South Asian (SAS) AF: 0.166 AC: 804 AN: 4830

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10616

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9432 AN: 68014

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.154 Hom.: 752

Bravo AF: 0.188

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	4.8
DANN	Benign	0.34
PhyloP100		-0.24
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: rs3748418; hg19: chr18-10468315;