chr7-92163781-G-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001161528.2(LRRD1):c.1422C>A(p.Asn474Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000812 in 1,354,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000081 ( 0 hom. )
Consequence
LRRD1
NM_001161528.2 missense
NM_001161528.2 missense
Scores
5
3
11
Clinical Significance
Conservation
PhyloP100: -0.0200
Genes affected
LRRD1 (HGNC:34300): (leucine rich repeats and death domain containing 1) Predicted to be involved in positive regulation of Ras protein signal transduction and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.932
BS2
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRRD1 | NM_001161528.2 | c.1422C>A | p.Asn474Lys | missense_variant | 2/6 | ENST00000458448.6 | NP_001155000.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRD1 | ENST00000458448.6 | c.1422C>A | p.Asn474Lys | missense_variant | 2/6 | 5 | NM_001161528.2 | ENSP00000405987.1 | ||
ENSG00000289027 | ENST00000692281.1 | c.2026-31909C>A | intron_variant | ENSP00000510568.1 | ||||||
ENSG00000285953 | ENST00000458493.6 | c.2026-4578C>A | intron_variant | 4 | ENSP00000396352.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000331 AC: 4AN: 121012Hom.: 0 AF XY: 0.0000155 AC XY: 1AN XY: 64470
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GnomAD4 exome AF: 0.00000812 AC: 11AN: 1354304Hom.: 0 Cov.: 30 AF XY: 0.00000899 AC XY: 6AN XY: 667108
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GnomAD4 genome Cov.: 33
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33
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2023 | The c.1422C>A (p.N474K) alteration is located in exon 1 (coding exon 1) of the LRRD1 gene. This alteration results from a C to A substitution at nucleotide position 1422, causing the asparagine (N) at amino acid position 474 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of methylation at N474 (P = 0.0082);Gain of methylation at N474 (P = 0.0082);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at