rs3735170

Variant names:

• chr7-150337095-T-C
• rs3735170
• NM_001142928.2:c.234T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001142928.2(LRRC61):​c.234T>C​(p.Ala78Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,612,716 control chromosomes in the GnomAD database, including 52,998 homozygotes. In-silico tool predicts 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 (4725 hom., cov: 33)
  • Exomes 𝑓: 0.25 (48273 hom.)
• Consequence: LRRC61 NM_001142928.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.03
• Publications: 29 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-5.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 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.234T>C	p.Ala78Ala	synonymous	Exon 3 of 3	NP_001136400.1
	LRRC61	NM_001363433.1		c.234T>C	p.Ala78Ala	synonymous	Exon 3 of 3	NP_001350362.1
	LRRC61	NM_001363434.1		c.234T>C	p.Ala78Ala	synonymous	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.234T>C	p.Ala78Ala	synonymous	Exon 3 of 3	ENSP00000352642.4
	LRRC61	ENST00000323078.7	TSL:1	c.234T>C	p.Ala78Ala	synonymous	Exon 2 of 2	ENSP00000339047.6
	LRRC61	ENST00000493307.1	TSL:5	c.234T>C	p.Ala78Ala	synonymous	Exon 4 of 4	ENSP00000420560.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37364 AN: 152104 Hom.: 4731 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.242 AC: 60448 AN: 249420 AF XY: 0.248

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.288

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.229

GnomAD4 exome AF: 0.254 AC: 371648 AN: 1460494 Hom.: 48273 Cov.: 36 AF XY: 0.256 AC XY: 185996 AN XY: 726674

African (AFR) AF: 0.245 AC: 8200 AN: 33480

American (AMR) AF: 0.113 AC: 5071 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8460 AN: 26130

East Asian (EAS) AF: 0.347 AC: 13768 AN: 39700

South Asian (SAS) AF: 0.280 AC: 24132 AN: 86258

European-Finnish (FIN) AF: 0.255 AC: 13274 AN: 52064

Middle Eastern (MID) AF: 0.242 AC: 1398 AN: 5768

European-Non Finnish (NFE) AF: 0.254 AC: 282113 AN: 1111982

Other (OTH) AF: 0.252 AC: 15232 AN: 60388

GnomAD4 genome AF: 0.246 AC: 37379 AN: 152222 Hom.: 4725 Cov.: 33 AF XY: 0.246 AC XY: 18329 AN XY: 74426

African (AFR) AF: 0.245 AC: 10177 AN: 41538

American (AMR) AF: 0.158 AC: 2424 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3472

East Asian (EAS) AF: 0.290 AC: 1498 AN: 5158

South Asian (SAS) AF: 0.283 AC: 1367 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2632 AN: 10604

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

European-Non Finnish (NFE) AF: 0.255 AC: 17308 AN: 67998

Other (OTH) AF: 0.223 AC: 471 AN: 2116

Alfa AF: 0.252 Hom.: 7000

Bravo AF: 0.235

Asia WGS AF: 0.282 AC: 985 AN: 3478

EpiCase AF: 0.257

EpiControl AF: 0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.023
DANN	Benign	0.33
PhyloP100		-5.0
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: rs3735170; hg19: chr7-150034184; COSMIC: COSV56230933; COSMIC: COSV56230933;