rs16940502

chr18-13430309-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.41-7935A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,294 control chromosomes in the GnomAD database, including 542 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 0.056 (542 hom., cov: 33)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDLRAD4	NM_001378100.1	c.41-7935A>G		intron_variant		ENST00000359446.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDLRAD4	ENST00000359446.11	c.41-7935A>G		intron_variant		1	NM_001378100.1	P1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8497 AN: 152176 Hom.: 538 Cov.: 33

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0606

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

GnomAD4 genome AF: 0.0559 AC: 8514 AN: 152294 Hom.: 542 Cov.: 33 AF XY: 0.0576 AC XY: 4287 AN XY: 74476

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.0819

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0362 Hom.: 204

Bravo AF: 0.0642

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.048
Dann	Benign	0.39

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: rs16940502; hg19: chr18-13430308;