rs12456874

Variant names:

• chr18-13366863-A-G
• rs12456874
• NM_001378100.1:c.-382-20478A>G

Variant summary

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

The NM_001378100.1(LDLRAD4):​c.-382-20478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,176 control chromosomes in the GnomAD database, including 3,584 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 0.20 (3584 hom., cov: 32)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923
• Publications: 12 publications found

Genes affected

LDLRAD4 (HGNC:1224): (low density lipoprotein receptor class A domain containing 4) Enables R-SMAD binding activity. Involved in negative regulation of cell migration; negative regulation of epithelial to mesenchymal transition; and negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway. Located in early endosome 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD4	NM_001378100.1	c.-382-20478A>G		intron_variant	Intron 2 of 6	ENST00000359446.11	NP_001365029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD4	ENST00000359446.11	c.-382-20478A>G		intron_variant	Intron 2 of 6	1	NM_001378100.1	ENSP00000352420.5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29883 AN: 152058 Hom.: 3587 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.196 AC: 29884 AN: 152176 Hom.: 3584 Cov.: 32 AF XY: 0.195 AC XY: 14493 AN XY: 74406

African (AFR) AF: 0.0674 AC: 2801 AN: 41554

American (AMR) AF: 0.230 AC: 3513 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1167 AN: 3472

East Asian (EAS) AF: 0.0375 AC: 194 AN: 5180

South Asian (SAS) AF: 0.275 AC: 1326 AN: 4828

European-Finnish (FIN) AF: 0.242 AC: 2564 AN: 10582

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17618 AN: 67970

Other (OTH) AF: 0.209 AC: 440 AN: 2108

Alfa AF: 0.242 Hom.: 21460

Bravo AF: 0.190

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.5
DANN	Benign	0.85
PhyloP100		0.92
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: rs12456874; hg19: chr18-13366862;