rs3735169

chr7-150337289-A-G

Variant summary

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

The NM_001142928.2(LRRC61):c.428A>G(p.Asn143Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,602,884 control chromosomes in the GnomAD database, including 52,699 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (4734 hom., cov: 33)
  • Exomes 𝑓: 0.25 (47965 hom.)
• Consequence: LRRC61 NM_001142928.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003939748).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC61	NM_001142928.2	c.428A>G	p.Asn143Ser	missense_variant	3/3	ENST00000359623.9
LRRC61	NM_001363433.1	c.428A>G	p.Asn143Ser	missense_variant	3/3
LRRC61	NM_001363434.1	c.428A>G	p.Asn143Ser	missense_variant	3/3
LRRC61	NM_023942.3	c.428A>G	p.Asn143Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC61	ENST00000359623.9	c.428A>G	p.Asn143Ser	missense_variant	3/3	2	NM_001142928.2	P1
LRRC61	ENST00000323078.7	c.428A>G	p.Asn143Ser	missense_variant	2/2	1		P1
LRRC61	ENST00000493307.1	c.428A>G	p.Asn143Ser	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37366 AN: 151758 Hom.: 4740 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.226

GnomAD3 exomes AF: 0.242 AC: 58797 AN: 242762 Hom.: 7658 AF XY: 0.248 AC XY: 32712 AN XY: 131998

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.288

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.254 AC: 369238 AN: 1451006 Hom.: 47965 Cov.: 36 AF XY: 0.256 AC XY: 184870 AN XY: 722294

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.246 AC: 37381 AN: 151878 Hom.: 4734 Cov.: 33 AF XY: 0.247 AC XY: 18320 AN XY: 74230

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.223

Alfa AF: 0.260 Hom.: 1527

Bravo AF: 0.236

TwinsUK AF: 0.247 AC: 917

ALSPAC AF: 0.251 AC: 966

ESP6500AA AF: 0.244 AC: 1076

ESP6500EA AF: 0.256 AC: 2198

ExAC AF: 0.249 AC: 30245

Asia WGS AF: 0.283 AC: 986 AN: 3474

EpiCase AF: 0.257

EpiControl AF: 0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.4
Dann	Benign	0.70
DEOGEN2	Benign	0.00014	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0077	N
MetaRNN	Benign	0.0039	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.5	N;N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.040	N;N;N
REVEL	Benign	0.015
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.017
MPC		0.15
ClinPred		0.00030	T
GERP RS		0.74
Varity_R		0.028
gMVP		0.17

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: rs3735169; hg19: chr7-150034378; COSMIC: COSV56230790; COSMIC: COSV56230790;