rs6505798

chr18-13308951-G-Achr18-13308951-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.-383+30763G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,112 control chromosomes in the GnomAD database, including 15,541 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 0.43 (15541 hom., cov: 33)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDLRAD4	NM_001378100.1	c.-383+30763G>A		intron_variant		ENST00000359446.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD4	ENST00000359446.11	c.-383+30763G>A		intron_variant		1	NM_001378100.1	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65934 AN: 151992 Hom.: 15520 Cov.: 33

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.434 AC: 66012 AN: 152112 Hom.: 15541 Cov.: 33 AF XY: 0.434 AC XY: 32254 AN XY: 74358

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.423

Alfa AF: 0.358 Hom.: 4735

Bravo AF: 0.446

Asia WGS AF: 0.463 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.18
Dann	Benign	0.32

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: rs6505798; hg19: chr18-13308950;