NM_001378100.1:c.-383+30763G>A

Variant names:

• chr18-13308951-G-A
• rs6505798
• NM_001378100.1:c.-383+30763G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378100.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD4	NM_001378100.1	MANE Select	c.-383+30763G>A		intron	N/A	NP_001365029.1
	LDLRAD4	NM_001378099.1		c.-383+30763G>A		intron	N/A	NP_001365028.1
	LDLRAD4	NM_001394662.1		c.-383+30763G>A		intron	N/A	NP_001381591.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD4	ENST00000359446.11	TSL:1 MANE Select	c.-383+30763G>A		intron	N/A	ENSP00000352420.5
	LDLRAD4	ENST00000399848.7	TSL:1	c.-383+30763G>A		intron	N/A	ENSP00000382741.2
	LDLRAD4	ENST00000679091.1		c.-383+30763G>A		intron	N/A	ENSP00000503185.1

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

African (AFR) AF: 0.634 AC: 26287 AN: 41480

American (AMR) AF: 0.407 AC: 6215 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1449 AN: 3466

East Asian (EAS) AF: 0.474 AC: 2457 AN: 5186

South Asian (SAS) AF: 0.435 AC: 2099 AN: 4822

European-Finnish (FIN) AF: 0.370 AC: 3909 AN: 10570

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22348 AN: 67980

Other (OTH) AF: 0.423 AC: 896 AN: 2116

Alfa AF: 0.358 Hom.: 5224

Bravo AF: 0.446

Asia WGS AF: 0.463 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.32
PhyloP100		-1.9
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: rs6505798; hg19: chr18-13308950;