rs35923425

Variant names:

• chr3-169851644-C-G
• rs35923425
• NM_024727.4:c.1134G>C

Variant summary

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

The NM_024727.4(LRRC31):​c.1134G>C​(p.Leu378Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 1,613,726 control chromosomes in the GnomAD database, including 4,249 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (339 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3910 hom.)
• Consequence: LRRC31 NM_024727.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 17 publications found

Genes affected

LRRC31 (HGNC:26261): (leucine rich repeat containing 31)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026362538).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC31	NM_024727.4	c.1134G>C	p.Leu378Phe	missense_variant	Exon 7 of 9	ENST00000316428.10	NP_079003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC31	ENST00000316428.10	c.1134G>C	p.Leu378Phe	missense_variant	Exon 7 of 9	1	NM_024727.4	ENSP00000325978.5
LRRC31	ENST00000523069.1	c.1134G>C	p.Leu378Phe	missense_variant	Exon 7 of 9	1		ENSP00000429145.1
LRRC31	ENST00000264676.9	c.966G>C	p.Leu322Phe	missense_variant	Exon 6 of 8	2		ENSP00000264676.5

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8986 AN: 152124 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0737

Gnomad OTH AF: 0.0775

GnomAD2 exomes AF: 0.0714 AC: 17819 AN: 249400 AF XY: 0.0725

Gnomad AFR exome AF: 0.0215

Gnomad AMR exome AF: 0.0971

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.0527

Gnomad FIN exome AF: 0.0285

Gnomad NFE exome AF: 0.0779

Gnomad OTH exome AF: 0.0780

GnomAD4 exome AF: 0.0701 AC: 102495 AN: 1461484 Hom.: 3910 Cov.: 31 AF XY: 0.0709 AC XY: 51581 AN XY: 727070

African (AFR) AF: 0.0217 AC: 727 AN: 33460

American (AMR) AF: 0.0996 AC: 4453 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2856 AN: 26132

East Asian (EAS) AF: 0.0320 AC: 1269 AN: 39694

South Asian (SAS) AF: 0.0730 AC: 6291 AN: 86234

European-Finnish (FIN) AF: 0.0319 AC: 1703 AN: 53420

Middle Eastern (MID) AF: 0.0895 AC: 516 AN: 5766

European-Non Finnish (NFE) AF: 0.0723 AC: 80336 AN: 1111692

Other (OTH) AF: 0.0719 AC: 4344 AN: 60380

GnomAD4 genome AF: 0.0591 AC: 9003 AN: 152242 Hom.: 339 Cov.: 32 AF XY: 0.0594 AC XY: 4419 AN XY: 74434

African (AFR) AF: 0.0238 AC: 988 AN: 41528

American (AMR) AF: 0.0956 AC: 1462 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3470

East Asian (EAS) AF: 0.0519 AC: 269 AN: 5188

South Asian (SAS) AF: 0.0734 AC: 354 AN: 4824

European-Finnish (FIN) AF: 0.0261 AC: 277 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0737 AC: 5013 AN: 68010

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.0758 Hom.: 354

Bravo AF: 0.0627

TwinsUK AF: 0.0774 AC: 287

ALSPAC AF: 0.0625 AC: 241

ESP6500AA AF: 0.0233 AC: 87

ESP6500EA AF: 0.0706 AC: 580

ExAC AF: 0.0694 AC: 8389

Asia WGS AF: 0.0910 AC: 316 AN: 3478

EpiCase AF: 0.0797

EpiControl AF: 0.0838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.78	T;T;T
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.9	H;.;H
PhyloP100		1.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.23
MutPred		0.29		Loss of glycosylation at S380 (P = 0.1166);.;Loss of glycosylation at S380 (P = 0.1166);
MPC		0.24
ClinPred		0.11	T
GERP RS		2.8
Varity_R		0.29
gMVP		0.74
Mutation Taster		=77/23	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: rs35923425; hg19: chr3-169569432; COSMIC: COSV107282124; COSMIC: COSV107282124;