rs2306034

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The NM_002334.4(LRP4):​c.*1850G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000861 in 152,102 control chromosomes in the GnomAD database, including 1 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 0.00086 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LRP4
NM_002334.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46
Variant links:
Genes affected
LRP4 (HGNC:6696): (LDL receptor related protein 4) This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]
LRP4-AS1 (HGNC:44128): (LRP4 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000861 (131/152102) while in subpopulation EAS AF= 0.021 (109/5180). AF 95% confidence interval is 0.0178. There are 1 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRP4NM_002334.4 linkuse as main transcriptc.*1850G>A 3_prime_UTR_variant 38/38 ENST00000378623.6
LRP4-AS1NR_038909.1 linkuse as main transcriptn.197+10416C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRP4ENST00000378623.6 linkuse as main transcriptc.*1850G>A 3_prime_UTR_variant 38/381 NM_002334.4 P1
LRP4-AS1ENST00000502049.3 linkuse as main transcriptn.192+10416C>T intron_variant, non_coding_transcript_variant 2
LRP4ENST00000529604.1 linkuse as main transcriptn.2511G>A non_coding_transcript_exon_variant 2/22
LRP4-AS1ENST00000531719.5 linkuse as main transcriptn.291+4187C>T intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000882
AC:
134
AN:
151984
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000266
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0216
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00144
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
440
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
270
Gnomad4 AFR exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000861
AC:
131
AN:
152102
Hom.:
1
Cov.:
32
AF XY:
0.00105
AC XY:
78
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0210
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00143
Alfa
AF:
0.000152
Hom.:
1
Bravo
AF:
0.00120
Asia WGS
AF:
0.00462
AC:
16
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
5.5
DANN
Benign
0.61

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2306034; hg19: chr11-46878684; API