rs74806847

Variant names:

• chr11-46868978-G-A
• rs74806847
• NM_002334.4:c.4837+10C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-46868978-G-A
• chr11-46868978-G-T

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.4837+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,614,064 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (164 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (145 hom.)
• Consequence: LRP4 NM_002334.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.242
• Publications: 0 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-AS1 (HGNC:44128): (LRP4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-46868978-G-A is Benign according to our data. Variant chr11-46868978-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 304854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002334.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP4	NM_002334.4	MANE Select	c.4837+10C>T		intron	N/A	NP_002325.2	O75096
	LRP4-AS1	NR_038909.1		n.198-4096G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP4	ENST00000378623.6	TSL:1 MANE Select	c.4837+10C>T		intron	N/A	ENSP00000367888.1	O75096
	LRP4	ENST00000858258.1		c.4288+10C>T		intron	N/A	ENSP00000528317.1
	LRP4-AS1	ENST00000502049.4	TSL:2	n.197-4096G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3869 AN: 152096 Hom.: 163 Cov.: 32

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00930

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0197

GnomAD2 exomes AF: 0.00627 AC: 1576 AN: 251366 AF XY: 0.00459

Gnomad AFR exome AF: 0.0875

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00243 AC: 3546 AN: 1461850 Hom.: 145 Cov.: 32 AF XY: 0.00207 AC XY: 1504 AN XY: 727232

African (AFR) AF: 0.0881 AC: 2949 AN: 33476

American (AMR) AF: 0.00438 AC: 196 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5766

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1112002

Other (OTH) AF: 0.00517 AC: 312 AN: 60394

GnomAD4 genome AF: 0.0255 AC: 3882 AN: 152214 Hom.: 164 Cov.: 32 AF XY: 0.0241 AC XY: 1796 AN XY: 74412

African (AFR) AF: 0.0884 AC: 3672 AN: 41520

American (AMR) AF: 0.00928 AC: 142 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68016

Other (OTH) AF: 0.0195 AC: 41 AN: 2106

Alfa AF: 0.0280 Hom.: 103

Bravo AF: 0.0288

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cenani-Lenz syndactyly syndrome (1)
-	-	1	Cenani-Lenz syndactyly syndrome;C3280402:Sclerosteosis 2;C4225377:Congenital myasthenic syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.78
PhyloP100		-0.24
Mutation Taster		=97/3	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: rs74806847; hg19: chr11-46890529;