18-13357201-A-G

Variant names:

• chr18-13357201-A-G
• rs981621
• NM_001378100.1:c.-382-30140A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378100.1(LDLRAD4):​c.-382-30140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,976 control chromosomes in the GnomAD database, including 12,589 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 0.40 (12589 hom., cov: 32)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLRAD4	NM_001378100.1	c.-382-30140A>G		intron_variant	Intron 2 of 6	ENST00000359446.11	NP_001365029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLRAD4	ENST00000359446.11	c.-382-30140A>G		intron_variant	Intron 2 of 6	1	NM_001378100.1	ENSP00000352420.5

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60885 AN: 151858 Hom.: 12581 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.401 AC: 60935 AN: 151976 Hom.: 12589 Cov.: 32 AF XY: 0.402 AC XY: 29854 AN XY: 74282

African (AFR) AF: 0.518 AC: 21454 AN: 41444

American (AMR) AF: 0.391 AC: 5979 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2401 AN: 5164

South Asian (SAS) AF: 0.403 AC: 1939 AN: 4810

European-Finnish (FIN) AF: 0.376 AC: 3961 AN: 10544

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22722 AN: 67958

Other (OTH) AF: 0.375 AC: 791 AN: 2112

Alfa AF: 0.250 Hom.: 605

Bravo AF: 0.408

Asia WGS AF: 0.442 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-1.7
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: rs981621; hg19: chr18-13357200;