6-53795288-A-C

Variant names:

• chr6-53795288-A-C
• rs201594887
• NM_018214.5:c.32A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018214.5(LRRC1):​c.32A>C​(p.Asn11Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,162 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N11S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC1 NM_018214.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.09
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.32A>C	p.Asn11Thr	missense	Exon 1 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.32A>C	p.Asn11Thr	missense	Exon 1 of 14	ENSP00000359925.1	Q9BTT6-1
	LRRC1	ENST00000960208.1		c.32A>C	p.Asn11Thr	missense	Exon 2 of 15	ENSP00000630267.1
	LRRC1	ENST00000370882.1	TSL:3	c.32A>C	p.Asn11Thr	missense	Exon 1 of 5	ENSP00000359919.1	Q5T0G3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460162 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726416

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111776

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.44		Gain of phosphorylation at N11 (P = 0.1514)
MVP		0.28
MPC		0.42
ClinPred		0.99	D
GERP RS		4.8
PromoterAI		-0.015	Neutral
Varity_R		0.70
gMVP		0.62
Mutation Taster		=56/44	polymorphism

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: rs201594887; hg19: chr6-53660086;