8-126556557-G-C

Variant names:

• chr8-126556557-G-C
• rs79248636
• NM_174911.5:c.833C>G

Variant summary

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

The NM_174911.5(LRATD2):​c.833C>G​(p.Pro278Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 1,606,746 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P278L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.020 (117 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (121 hom.)
• Consequence: LRATD2 NM_174911.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 2 publications found

Genes affected

LRATD2 (HGNC:24166): (LRAT domain containing 2) Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016130209).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRATD2	NM_174911.5	c.833C>G	p.Pro278Arg	missense_variant	Exon 2 of 2	ENST00000304916.4	NP_777571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRATD2	ENST00000304916.4	c.833C>G	p.Pro278Arg	missense_variant	Exon 2 of 2	1	NM_174911.5	ENSP00000302578.3
LRATD2	ENST00000652209.1	c.833C>G	p.Pro278Arg	missense_variant	Exon 1 of 1			ENSP00000498944.1
PCAT1	ENST00000524320.2	n.235G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
LRATD2	ENST00000517458.1	n.-138C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3083 AN: 152258 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00490 AC: 1131 AN: 230868 AF XY: 0.00366

Gnomad AFR exome AF: 0.0755

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000214

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.00207 AC: 3008 AN: 1454370 Hom.: 121 Cov.: 31 AF XY: 0.00173 AC XY: 1251 AN XY: 723030

African (AFR) AF: 0.0732 AC: 2431 AN: 33196

American (AMR) AF: 0.00323 AC: 141 AN: 43650

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39448

South Asian (SAS) AF: 0.000188 AC: 16 AN: 85316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51846

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5748

European-Non Finnish (NFE) AF: 0.0000811 AC: 90 AN: 1109258

Other (OTH) AF: 0.00527 AC: 316 AN: 60004

GnomAD4 genome AF: 0.0203 AC: 3091 AN: 152376 Hom.: 117 Cov.: 33 AF XY: 0.0198 AC XY: 1475 AN XY: 74510

African (AFR) AF: 0.0712 AC: 2962 AN: 41584

American (AMR) AF: 0.00640 AC: 98 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.00162 Hom.: 2

Bravo AF: 0.0226

ESP6500AA AF: 0.0635 AC: 277

ESP6500EA AF: 0.000235 AC: 2

ExAC AF: 0.00651 AC: 783

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.061
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.024	D
Polyphen		0.24	B
Vest4		0.20
MVP		0.61
MPC		0.79
ClinPred		0.016	T
GERP RS		4.0
Varity_R		0.11
gMVP		0.18
Mutation Taster		=99/1	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: rs79248636; hg19: chr8-127568802;