4-51995168-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001024611.3(LRRC66):c.1854G>A(p.Met618Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,614,242 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M618T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001024611.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRC66 | ENST00000682860.1 | c.1854G>A | p.Met618Ile | missense_variant | Exon 5 of 5 | NM_001024611.3 | ENSP00000508002.1 | |||
LRRC66 | ENST00000343457.3 | c.1854G>A | p.Met618Ile | missense_variant | Exon 4 of 4 | 1 | ENSP00000341944.3 |
Frequencies
GnomAD3 genomes AF: 0.000190 AC: 29AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000357 AC: 89AN: 249434Hom.: 0 AF XY: 0.000443 AC XY: 60AN XY: 135324
GnomAD4 exome AF: 0.000279 AC: 408AN: 1461890Hom.: 4 Cov.: 31 AF XY: 0.000336 AC XY: 244AN XY: 727248
GnomAD4 genome AF: 0.000190 AC: 29AN: 152352Hom.: 0 Cov.: 32 AF XY: 0.000174 AC XY: 13AN XY: 74506
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1854G>A (p.M618I) alteration is located in exon 5 (coding exon 4) of the LRRC66 gene. This alteration results from a G to A substitution at nucleotide position 1854, causing the methionine (M) at amino acid position 618 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at