rs12456874

chr18-13366863-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LDLRAD4	NM_001378100.1	c.-382-20478A>G		intron_variant		ENST00000359446.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD4	ENST00000359446.11	c.-382-20478A>G		intron_variant		1	NM_001378100.1	P1

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

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.209

Alfa AF: 0.253 Hom.: 10258

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12456874; hg19: chr18-13366862;