chr18-13539694-A-G

Position:

• chr18-13539694-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.182-81423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,904 control chromosomes in the GnomAD database, including 16,839 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 0.45 (16839 hom., cov: 31)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD4	NM_001378100.1	c.182-81423A>G		intron_variant		ENST00000359446.11	NP_001365029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD4	ENST00000359446.11	c.182-81423A>G		intron_variant		1	NM_001378100.1	ENSP00000352420	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68353 AN: 151786 Hom.: 16831 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.450 AC: 68381 AN: 151904 Hom.: 16839 Cov.: 31 AF XY: 0.457 AC XY: 33943 AN XY: 74206

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.436

Alfa AF: 0.444 Hom.: 2279

Bravo AF: 0.448

Asia WGS AF: 0.596 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.42

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: rs7507114; hg19: chr18-13539693;