chr18-13438906-A-G

Variant names:

• chr18-13438906-A-G
• rs8096897
• NM_001378100.1:c.181+522A>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.181+522A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 152,318 control chromosomes in the GnomAD database, including 268 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 0.032 (268 hom., cov: 33)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 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.181+522A>G		intron	N/A	NP_001365029.1
	LDLRAD4	NM_001378098.1		c.181+522A>G		intron	N/A	NP_001365027.1
	LDLRAD4	NM_001378099.1		c.181+522A>G		intron	N/A	NP_001365028.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD4	ENST00000359446.11	TSL:1 MANE Select	c.181+522A>G		intron	N/A	ENSP00000352420.5
	LDLRAD4	ENST00000399848.7	TSL:1	c.181+522A>G		intron	N/A	ENSP00000382741.2
	LDLRAD4	ENST00000679091.1		c.181+522A>G		intron	N/A	ENSP00000503185.1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4816 AN: 152200 Hom.: 268 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0317 AC: 4821 AN: 152318 Hom.: 268 Cov.: 33 AF XY: 0.0304 AC XY: 2261 AN XY: 74478

African (AFR) AF: 0.110 AC: 4569 AN: 41550

American (AMR) AF: 0.0120 AC: 183 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68040

Other (OTH) AF: 0.0227 AC: 48 AN: 2110

Alfa AF: 0.0120 Hom.: 121

Bravo AF: 0.0361

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.25
PhyloP100		-0.047
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: rs8096897; hg19: chr18-13438905;