11-46883767-A-T

Variant names:

• chr11-46883767-A-T
• rs17790156
• NM_002334.4:c.2612+104T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002334.4(LRP4):​c.2612+104T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 881,900 control chromosomes in the GnomAD database, including 3,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (622 hom., cov: 33)
  • Exomes 𝑓: 0.093 (3307 hom.)
• Consequence: LRP4 NM_002334.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.348
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-46883767-A-T is Benign according to our data. Variant chr11-46883767-A-T is described in ClinVar as Benign. ClinVar VariationId is 1297981.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP4	NM_002334.4	c.2612+104T>A		intron_variant	Intron 19 of 37	ENST00000378623.6	NP_002325.2
LRP4	XM_017017734.2	c.2612+104T>A		intron_variant	Intron 19 of 38		XP_016873223.1
LRP4	XM_011520103.3	c.1808+104T>A		intron_variant	Intron 13 of 31		XP_011518405.1
LRP4	XM_011520104.3	c.377+104T>A		intron_variant	Intron 4 of 22		XP_011518406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP4	ENST00000378623.6	c.2612+104T>A		intron_variant	Intron 19 of 37	1	NM_002334.4	ENSP00000367888.1
LRP4	ENST00000529921.1	n.*157T>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13563 AN: 152128 Hom.: 624 Cov.: 33

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0856

GnomAD4 exome AF: 0.0928 AC: 67690 AN: 729654 Hom.: 3307 AF XY: 0.0919 AC XY: 34740 AN XY: 377874

African (AFR) AF: 0.0873 AC: 1685 AN: 19292

American (AMR) AF: 0.0462 AC: 1479 AN: 32046

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 1345 AN: 18012

East Asian (EAS) AF: 0.0841 AC: 2884 AN: 34298

South Asian (SAS) AF: 0.0669 AC: 4014 AN: 59990

European-Finnish (FIN) AF: 0.0654 AC: 2852 AN: 43620

Middle Eastern (MID) AF: 0.0783 AC: 212 AN: 2706

European-Non Finnish (NFE) AF: 0.103 AC: 49856 AN: 483954

Other (OTH) AF: 0.0941 AC: 3363 AN: 35736

GnomAD4 genome AF: 0.0891 AC: 13570 AN: 152246 Hom.: 622 Cov.: 33 AF XY: 0.0870 AC XY: 6473 AN XY: 74444

African (AFR) AF: 0.0867 AC: 3600 AN: 41538

American (AMR) AF: 0.0710 AC: 1086 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.0995 AC: 515 AN: 5178

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4824

European-Finnish (FIN) AF: 0.0634 AC: 673 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6866 AN: 68012

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.0409 Hom.: 30

Bravo AF: 0.0892

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.54
PhyloP100		-0.35
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: rs17790156; hg19: chr11-46905318; COSMIC: COSV66138586; COSMIC: COSV66138586;