rs3735170

Positions:

• chr7-150337095-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC61	NM_001142928.2	c.234T>C	p.Ala78Ala	synonymous_variant	3/3	ENST00000359623.9	NP_001136400.1
LRRC61	NM_001363433.1	c.234T>C	p.Ala78Ala	synonymous_variant	3/3		NP_001350362.1
LRRC61	NM_001363434.1	c.234T>C	p.Ala78Ala	synonymous_variant	3/3		NP_001350363.1
LRRC61	NM_023942.3	c.234T>C	p.Ala78Ala	synonymous_variant	2/2		NP_076431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC61	ENST00000359623.9	c.234T>C	p.Ala78Ala	synonymous_variant	3/3	2	NM_001142928.2	ENSP00000352642.4
LRRC61	ENST00000323078.7	c.234T>C	p.Ala78Ala	synonymous_variant	2/2	1		ENSP00000339047.6
LRRC61	ENST00000493307.1	c.234T>C	p.Ala78Ala	synonymous_variant	4/4	5		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

GnomAD3 exomes AF: 0.242 AC: 60448 AN: 249420 Hom.: 7902 AF XY: 0.248 AC XY: 33531 AN XY: 135202

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 SAS exome AF: 0.283

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

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.252

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

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.223

Alfa AF: 0.254 Hom.: 5418

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.023
DANN	Benign	0.33

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: rs3735170; hg19: chr7-150034184; COSMIC: COSV56230933; COSMIC: COSV56230933;