rs16940502

Variant names:

• chr18-13430309-A-G
• rs16940502
• NM_001378100.1:c.41-7935A>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.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
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD4	NM_001378100.1	MANE Select	c.41-7935A>G		intron	N/A	NP_001365029.1	O15165-1
	LDLRAD4	NM_001378098.1		c.41-7935A>G		intron	N/A	NP_001365027.1	O15165-1
	LDLRAD4	NM_001378099.1		c.41-7935A>G		intron	N/A	NP_001365028.1	O15165-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD4	ENST00000359446.11	TSL:1 MANE Select	c.41-7935A>G		intron	N/A	ENSP00000352420.5	O15165-1
	LDLRAD4	ENST00000399848.7	TSL:1	c.41-7935A>G		intron	N/A	ENSP00000382741.2	O15165-2
	LDLRAD4	ENST00000679091.1		c.41-7935A>G		intron	N/A	ENSP00000503185.1	O15165-1

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

African (AFR) AF: 0.0759 AC: 3154 AN: 41562

American (AMR) AF: 0.0787 AC: 1205 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.338 AC: 1748 AN: 5178

South Asian (SAS) AF: 0.0819 AC: 395 AN: 4822

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0256 AC: 1741 AN: 68020

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0408 Hom.: 873

Bravo AF: 0.0642

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.39
PhyloP100		-1.0
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: rs16940502; hg19: chr18-13430308;