chr3-169800667-T-C

Position:

• chr3-169800667-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172779.2(LRRC34):​c.745A>G​(p.Ser249Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,524,046 control chromosomes in the GnomAD database, including 73,257 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8949 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64308 hom.)
• Consequence: LRRC34 NM_001172779.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

Genes affected

LRRC34 (HGNC:28408): (leucine rich repeat containing 34) Predicted to be involved in cell differentiation. Predicted to be located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

LRRC34 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6204407E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC34	NM_001172779.2	c.745A>G	p.Ser249Gly	missense_variant	7/11	ENST00000446859.7	NP_001166250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC34	ENST00000446859.7	c.745A>G	p.Ser249Gly	missense_variant	7/11	2	NM_001172779.2	ENSP00000414635.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50201 AN: 151916 Hom.: 8924 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.337

GnomAD3 exomes AF: 0.369 AC: 49029 AN: 132890 Hom.: 10529 AF XY: 0.359 AC XY: 25934 AN XY: 72330

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.687

Gnomad SAS exome AF: 0.362

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.292 AC: 400521 AN: 1372012 Hom.: 64308 Cov.: 29 AF XY: 0.294 AC XY: 199537 AN XY: 677604

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.331 AC: 50275 AN: 152034 Hom.: 8949 Cov.: 32 AF XY: 0.334 AC XY: 24857 AN XY: 74342

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.340

Alfa AF: 0.281 Hom.: 10794

Bravo AF: 0.349

TwinsUK AF: 0.249 AC: 925

ALSPAC AF: 0.269 AC: 1036

ExAC AF: 0.304 AC: 4538

Asia WGS AF: 0.512 AC: 1776 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	18
DANN	Benign	0.58
DEOGEN2	Benign	0.0093	T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.039	T;T
MetaRNN	Benign	0.0000026	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.043
Sift	Benign	0.46	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0010	.;B
Vest4		0.064
MPC		0.057
ClinPred		0.0021	T
GERP RS		3.4
Varity_R		0.11
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6793295; hg19: chr3-169518455; COSMIC: COSV57186839; COSMIC: COSV57186839;