rs898604

chr11-46896432-G-Achr11-46896432-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002334.4(LRP4):c.923-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,497,470 control chromosomes in the GnomAD database, including 497,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44816 hom., cov: 33)
  • Exomes 𝑓: 0.81 (452201 hom.)
• Consequence: LRP4 NM_002334.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.373

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-46896432-G-A is Benign according to our data. Variant chr11-46896432-G-A is described in ClinVar as [Benign]. Clinvar id is 1227084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP4	NM_002334.4	c.923-97C>T		intron_variant		ENST00000378623.6
LRP4	XM_011520103.3	c.119-97C>T		intron_variant
LRP4	XM_017017734.2	c.923-97C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP4	ENST00000378623.6	c.923-97C>T		intron_variant		1	NM_002334.4	P1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115512 AN: 152028 Hom.: 44793 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.814 AC: 1094744 AN: 1345324 Hom.: 452201 AF XY: 0.814 AC XY: 548214 AN XY: 673198

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.898

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.770

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.847

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome AF: 0.760 AC: 115585 AN: 152146 Hom.: 44816 Cov.: 33 AF XY: 0.752 AC XY: 55981 AN XY: 74394

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.796

Alfa AF: 0.832 Hom.: 89340

Bravo AF: 0.749

Asia WGS AF: 0.650 AC: 2262 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	9.6
Dann	Benign	0.68

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: rs898604; hg19: chr11-46917983; COSMIC: COSV66136184; COSMIC: COSV66136184;