11-46857156-TAC-T

Position:

• chr11-46857156-TAC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002334.4(LRP4):​c.*1825_*1826del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 152,208 control chromosomes in the GnomAD database, including 157 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (157 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRP4 NM_002334.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157

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)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-46857156-TAC-T is Benign according to our data. Variant chr11-46857156-TAC-T is described in ClinVar as [Likely_benign]. Clinvar id is 304827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP4	NM_002334.4	c.*1825_*1826del		3_prime_UTR_variant	38/38	ENST00000378623.6
LRP4-AS1	NR_038909.1	n.197+10440_197+10441del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP4	ENST00000378623.6	c.*1825_*1826del		3_prime_UTR_variant	38/38	1	NM_002334.4	P1
LRP4-AS1	ENST00000502049.3	n.192+10440_192+10441del		intron_variant, non_coding_transcript_variant		2
LRP4	ENST00000529604.1	n.2486_2487del		non_coding_transcript_exon_variant	2/2	2
LRP4-AS1	ENST00000531719.5	n.291+4211_291+4212del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3855 AN: 152090 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00930

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0197

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 412 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 254

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: 0.0254 AC: 3868 AN: 152208 Hom.: 157 Cov.: 32 AF XY: 0.0241 AC XY: 1797 AN XY: 74428

Gnomad4 AFR AF: 0.0882

Gnomad4 AMR AF: 0.00928

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0191 Hom.: 10

Bravo AF: 0.0288

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cenani-Lenz syndactyly syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs147363340; hg19: chr11-46878707;