rs17608293

Positions:

• chr18-13378637-G-A
• chr18-13378637-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378100.1(LDLRAD4):​c.-382-8704G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,960 control chromosomes in the GnomAD database, including 7,243 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 0.28 (7243 hom., cov: 32)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.818

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]

LDLRAD4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD4	NM_001378100.1	c.-382-8704G>A		intron_variant		ENST00000359446.11	NP_001365029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD4	ENST00000359446.11	c.-382-8704G>A		intron_variant		1	NM_001378100.1	ENSP00000352420.5

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42627 AN: 151842 Hom.: 7235 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.281 AC: 42647 AN: 151960 Hom.: 7243 Cov.: 32 AF XY: 0.279 AC XY: 20722 AN XY: 74266

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.301

Alfa AF: 0.330 Hom.: 3098

Bravo AF: 0.269

Asia WGS AF: 0.246 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.2
DANN	Benign	0.46

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: rs17608293; hg19: chr18-13378636;