6-53902634-C-T

Variant names:

• chr6-53902634-C-T
• rs372298061
• NM_018214.5:c.793C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018214.5(LRRC1):​c.793C>T​(p.Leu265Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LRRC1 NM_018214.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

Genes affected

LRRC1 (HGNC:14307): (leucine rich repeat containing 1) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018214.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC1	NM_018214.5	MANE Select	c.793C>T	p.Leu265Leu	synonymous	Exon 9 of 14	NP_060684.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC1	ENST00000370888.6	TSL:1 MANE Select	c.793C>T	p.Leu265Leu	synonymous	Exon 9 of 14	ENSP00000359925.1	Q9BTT6-1
	LRRC1	ENST00000960208.1		c.793C>T	p.Leu265Leu	synonymous	Exon 10 of 15	ENSP00000630267.1
	LRRC1	ENST00000487251.5	TSL:2	n.*195C>T		non_coding_transcript_exon	Exon 10 of 11	ENSP00000435217.1	Q9BTT6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424040 Hom.: 0 Cov.: 27 AF XY: 0.00000141 AC XY: 1 AN XY: 708080

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32220

American (AMR) AF: 0.00 AC: 0 AN: 39626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25148

East Asian (EAS) AF: 0.00 AC: 0 AN: 39204

South Asian (SAS) AF: 0.00 AC: 0 AN: 78848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091370

Other (OTH) AF: 0.00 AC: 0 AN: 58958

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		1.7

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: rs372298061; hg19: chr6-53767432;