rs3741792

Variant names:

• chr12-12117026-G-A
• rs3741792
• ENST00000538239.5:n.*2379C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-12117026-G-A
• chr12-12117026-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538239.5(LRP6):​n.*2379C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 152,186 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.048 (251 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LRP6 ENST00000538239.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 8 publications found

Genes affected

LRP6 (HGNC:6698): (LDL receptor related protein 6) This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been determined.[provided by RefSeq, Dec 2009]

BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP6	NM_002336.3	c.*4100C>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000261349.9	NP_002327.2
LRP6	NR_182264.1	n.7530C>T		non_coding_transcript_exon_variant	Exon 25 of 25
LRP6	XR_002957325.2	n.8212C>T		non_coding_transcript_exon_variant	Exon 24 of 24
LRP6	XM_047428844.1	c.*4100C>T		3_prime_UTR_variant	Exon 21 of 21		XP_047284800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP6	ENST00000538239.5	n.*2379C>T		non_coding_transcript_exon_variant	Exon 24 of 24	1		ENSP00000445083.1
LRP6	ENST00000261349.9	c.*4100C>T		3_prime_UTR_variant	Exon 23 of 23	1	NM_002336.3	ENSP00000261349.4
LRP6	ENST00000538239.5	n.*2379C>T		3_prime_UTR_variant	Exon 24 of 24	1		ENSP00000445083.1
BCL2L14	ENST00000298566.2	n.711+1699G>A		intron_variant	Intron 4 of 6	2		ENSP00000298566.1

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7306 AN: 152068 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0186

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.0777

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0664

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0480 AC: 7304 AN: 152186 Hom.: 251 Cov.: 32 AF XY: 0.0487 AC XY: 3620 AN XY: 74390

African (AFR) AF: 0.0158 AC: 656 AN: 41546

American (AMR) AF: 0.0469 AC: 717 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5190

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4818

European-Finnish (FIN) AF: 0.0777 AC: 821 AN: 10572

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0634 AC: 4309 AN: 67984

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0609 Hom.: 464

Bravo AF: 0.0465

Asia WGS AF: 0.0200 AC: 71 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.62
DANN	Benign	0.68
PhyloP100		-0.38
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: rs3741792; hg19: chr12-12269960;