3-169800667-T-C

Variant names:

• chr3-169800667-T-C
• rs6793295
• NM_001172779.2:c.745A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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
• Publications: 77 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRRC34	NM_001172779.2	c.745A>G	p.Ser249Gly	missense_variant	Exon 7 of 11	ENST00000446859.7	NP_001166250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC34	ENST00000446859.7	c.745A>G	p.Ser249Gly	missense_variant	Exon 7 of 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

GnomAD2 exomes AF: 0.369 AC: 49029 AN: 132890 AF XY: 0.359

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 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

African (AFR) AF: 0.383 AC: 11981 AN: 31298

American (AMR) AF: 0.518 AC: 18275 AN: 35260

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 5837 AN: 25088

East Asian (EAS) AF: 0.713 AC: 25331 AN: 35516

South Asian (SAS) AF: 0.365 AC: 28641 AN: 78410

European-Finnish (FIN) AF: 0.286 AC: 9692 AN: 33860

Middle Eastern (MID) AF: 0.337 AC: 1744 AN: 5178

European-Non Finnish (NFE) AF: 0.263 AC: 281388 AN: 1070004

Other (OTH) AF: 0.307 AC: 17632 AN: 57398

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

African (AFR) AF: 0.391 AC: 16219 AN: 41452

American (AMR) AF: 0.393 AC: 6001 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3472

East Asian (EAS) AF: 0.685 AC: 3542 AN: 5172

South Asian (SAS) AF: 0.363 AC: 1753 AN: 4828

European-Finnish (FIN) AF: 0.274 AC: 2896 AN: 10562

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18073 AN: 67958

Other (OTH) AF: 0.340 AC: 718 AN: 2110

Alfa AF: 0.294 Hom.: 26576

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
PhyloP100		2.7
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6793295; hg19: chr3-169518455; COSMIC: COSV57186839; COSMIC: COSV57186839;