NM_001142928.2:c.428A>G

Variant names:

• chr7-150337289-A-G
• rs3735169
• NM_001142928.2:c.428A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 0.25 (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
• Publications: 33 publications found

Genes affected

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

ENSG00000301866 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142928.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC61	NM_001142928.2	MANE Select	c.428A>G	p.Asn143Ser	missense	Exon 3 of 3	NP_001136400.1
	LRRC61	NM_001363433.1		c.428A>G	p.Asn143Ser	missense	Exon 3 of 3	NP_001350362.1
	LRRC61	NM_001363434.1		c.428A>G	p.Asn143Ser	missense	Exon 3 of 3	NP_001350363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC61	ENST00000359623.9	TSL:2 MANE Select	c.428A>G	p.Asn143Ser	missense	Exon 3 of 3	ENSP00000352642.4
	LRRC61	ENST00000323078.7	TSL:1	c.428A>G	p.Asn143Ser	missense	Exon 2 of 2	ENSP00000339047.6
	LRRC61	ENST00000493307.1	TSL:5	c.428A>G	p.Asn143Ser	missense	Exon 4 of 4	ENSP00000420560.1

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

GnomAD2 exomes AF: 0.242 AC: 58797 AN: 242762 AF XY: 0.248

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 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

African (AFR) AF: 0.245 AC: 8205 AN: 33472

American (AMR) AF: 0.113 AC: 5060 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8460 AN: 26126

East Asian (EAS) AF: 0.348 AC: 13795 AN: 39678

South Asian (SAS) AF: 0.280 AC: 24120 AN: 86246

European-Finnish (FIN) AF: 0.256 AC: 10999 AN: 42900

Middle Eastern (MID) AF: 0.242 AC: 1398 AN: 5766

European-Non Finnish (NFE) AF: 0.254 AC: 281994 AN: 1111806

Other (OTH) AF: 0.252 AC: 15207 AN: 60302

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

African (AFR) AF: 0.246 AC: 10194 AN: 41388

American (AMR) AF: 0.159 AC: 2422 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1500 AN: 5138

South Asian (SAS) AF: 0.284 AC: 1363 AN: 4804

European-Finnish (FIN) AF: 0.249 AC: 2631 AN: 10568

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17298 AN: 67922

Other (OTH) AF: 0.223 AC: 469 AN: 2104

Alfa AF: 0.257 Hom.: 2332

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 v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-0.26
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.015
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.017
MPC		0.15
ClinPred		0.00030	T
GERP RS		0.74
Varity_R		0.028
gMVP		0.17
Mutation Taster		=100/0	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: rs3735169; hg19: chr7-150034378; COSMIC: COSV56230790; COSMIC: COSV56230790;