rs898604

Variant names:

• chr11-46896432-G-A
• rs898604
• NM_002334.4:c.923-97C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-46896432-G-A
• chr11-46896432-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.373
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• Cenani-Lenz syndactyly syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• congenital myasthenic syndrome 17

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sclerosteosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sclerosteosis 2

  Inheritance: SD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1227084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
LRP4	NM_002334.4	c.923-97C>T		intron_variant	Intron 8 of 37	ENST00000378623.6	NP_002325.2
LRP4	XM_017017734.2	c.923-97C>T		intron_variant	Intron 8 of 38		XP_016873223.1
LRP4	XM_011520103.3	c.119-97C>T		intron_variant	Intron 2 of 31		XP_011518405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP4	ENST00000378623.6	c.923-97C>T		intron_variant	Intron 8 of 37	1	NM_002334.4	ENSP00000367888.1

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

African (AFR) AF: 0.680 AC: 21213 AN: 31194

American (AMR) AF: 0.592 AC: 25924 AN: 43802

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 22510 AN: 25058

East Asian (EAS) AF: 0.374 AC: 14573 AN: 38942

South Asian (SAS) AF: 0.770 AC: 63760 AN: 82834

European-Finnish (FIN) AF: 0.774 AC: 29879 AN: 38618

Middle Eastern (MID) AF: 0.847 AC: 4672 AN: 5514

European-Non Finnish (NFE) AF: 0.847 AC: 866400 AN: 1022742

Other (OTH) AF: 0.809 AC: 45813 AN: 56620

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

African (AFR) AF: 0.672 AC: 27860 AN: 41486

American (AMR) AF: 0.711 AC: 10876 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3111 AN: 3472

East Asian (EAS) AF: 0.386 AC: 1992 AN: 5164

South Asian (SAS) AF: 0.768 AC: 3702 AN: 4820

European-Finnish (FIN) AF: 0.743 AC: 7871 AN: 10596

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57417 AN: 67990

Other (OTH) AF: 0.796 AC: 1683 AN: 2114

Alfa AF: 0.816 Hom.: 143661

Bravo AF: 0.749

Asia WGS AF: 0.650 AC: 2262 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.6
DANN	Benign	0.68
PhyloP100		0.37
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: rs898604; hg19: chr11-46917983; COSMIC: COSV66136184; COSMIC: COSV66136184;