18-13512267-C-T

Variant names:

• chr18-13512267-C-T
• rs1785205
• NM_001378100.1:c.181+73883C>T

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+73883C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,996 control chromosomes in the GnomAD database, including 31,348 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 0.63 (31348 hom., cov: 32)
• Consequence: LDLRAD4 NM_001378100.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 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.181+73883C>T		intron	N/A	NP_001365029.1	O15165-1
	LDLRAD4	NM_001378098.1		c.181+73883C>T		intron	N/A	NP_001365027.1	O15165-1
	LDLRAD4	NM_001378099.1		c.181+73883C>T		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.181+73883C>T		intron	N/A	ENSP00000352420.5	O15165-1
	LDLRAD4	ENST00000399848.7	TSL:1	c.181+73883C>T		intron	N/A	ENSP00000382741.2	O15165-2
	LDLRAD4	ENST00000679091.1		c.181+73883C>T		intron	N/A	ENSP00000503185.1	O15165-1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96261 AN: 151878 Hom.: 31325 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.634 AC: 96324 AN: 151996 Hom.: 31348 Cov.: 32 AF XY: 0.635 AC XY: 47201 AN XY: 74314

African (AFR) AF: 0.485 AC: 20073 AN: 41392

American (AMR) AF: 0.706 AC: 10775 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1957 AN: 3470

East Asian (EAS) AF: 0.726 AC: 3759 AN: 5180

South Asian (SAS) AF: 0.730 AC: 3515 AN: 4818

European-Finnish (FIN) AF: 0.693 AC: 7331 AN: 10572

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46812 AN: 67988

Other (OTH) AF: 0.616 AC: 1298 AN: 2108

Alfa AF: 0.660 Hom.: 102490

Bravo AF: 0.628

Asia WGS AF: 0.701 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		0.032
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: rs1785205; hg19: chr18-13512266;