chr7-92163781-G-T

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

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200
Variant links:
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]

Genome browser will be placed here

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
LRRD1NM_001161528.2 linkuse as main transcriptc.1422C>A p.Asn474Lys missense_variant 2/6 ENST00000458448.6 NP_001155000.1 A4D1F6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRD1ENST00000458448.6 linkuse as main transcriptc.1422C>A p.Asn474Lys missense_variant 2/65 NM_001161528.2 ENSP00000405987.1 A4D1F6-1
ENSG00000289027ENST00000692281.1 linkuse as main transcriptc.2026-31909C>A intron_variant ENSP00000510568.1 A0A8I5KWQ7
ENSG00000285953ENST00000458493.6 linkuse as main transcriptc.2026-4578C>A intron_variant 4 ENSP00000396352.2 C9JD81

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000331
AC:
4
AN:
121012
Hom.:
0
AF XY:
0.0000155
AC XY:
1
AN XY:
64470
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000449
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000812
AC:
11
AN:
1354304
Hom.:
0
Cov.:
30
AF XY:
0.00000899
AC XY:
6
AN XY:
667108
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000226
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.41e-7
Gnomad4 OTH exome
AF:
0.0000357
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000453

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 submitterclinical testingAmbry GeneticsMar 22, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
0.13
Eigen_PC
Benign
-0.024
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.66
.;T
M_CAP
Benign
0.039
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Benign
-0.57
T
MutationAssessor
Pathogenic
4.5
H;H
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-5.1
D;D
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.070
T;T
Polyphen
1.0
D;D
Vest4
0.75
MutPred
0.82
Gain of methylation at N474 (P = 0.0082);Gain of methylation at N474 (P = 0.0082);
MVP
0.099
ClinPred
0.85
D
GERP RS
-0.53
Varity_R
0.47
gMVP
0.60

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1199043595; hg19: chr7-91793095; API