19-33208703-G-A

Position:

• chr19-33208703-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002333.4(LRP3):​c.*1128G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 710,012 control chromosomes in the GnomAD database, including 2,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1541 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1147 hom.)
• Consequence: LRP3 NM_002333.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.18

Genes affected

LRP3 (HGNC:6695): (LDL receptor related protein 3) Involved in negative regulation of fat cell differentiation; positive regulation of osteoblast differentiation; and regulation of gene expression. Predicted to be located in clathrin-coated pit. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A10 (HGNC:11058): (solute carrier family 7 member 10) SLC7A10, in association with 4F2HC (SLC3A2; MIM 158070), mediates high-affinity transport of D-serine and several other neutral amino acids (Nakauchi et al., 2000 [PubMed 10863037]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 19-33208703-G-A is Benign according to our data. Variant chr19-33208703-G-A is described in ClinVar as [Benign]. Clinvar id is 1253365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP3	NM_002333.4	c.*1128G>A		3_prime_UTR_variant	7/7	ENST00000253193.9	NP_002324.2
SLC7A10	NM_019849.3	c.*188C>T		3_prime_UTR_variant	11/11	ENST00000253188.8	NP_062823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP3	ENST00000253193.9	c.*1128G>A		3_prime_UTR_variant	7/7	1	NM_002333.4	ENSP00000253193.6
SLC7A10	ENST00000253188.8	c.*188C>T		3_prime_UTR_variant	11/11	1	NM_019849.3	ENSP00000253188.2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15302 AN: 152030 Hom.: 1527 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0484 AC: 26990 AN: 557864 Hom.: 1147 Cov.: 7 AF XY: 0.0500 AC XY: 14684 AN XY: 293874

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.0371

Gnomad4 ASJ exome AF: 0.0344

Gnomad4 EAS exome AF: 0.0359

Gnomad4 SAS exome AF: 0.0956

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.0376

Gnomad4 OTH exome AF: 0.0612

GnomAD4 genome AF: 0.101 AC: 15347 AN: 152148 Hom.: 1541 Cov.: 33 AF XY: 0.0983 AC XY: 7309 AN XY: 74388

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0377

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0365

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0713 Hom.: 115

Bravo AF: 0.110

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.91

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: rs11542481; hg19: chr19-33699609;