Variant chr7-92163489-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001161528.2(LRRD1):c.1714C>T(p.Pro572Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000582 in 1,375,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

LRRD1
NM_001161528.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.72

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]

LRRD1 links:

ENSG00000289027 (HGNC:):

ENSG00000289027 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36475214).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRD1	NM_001161528.2 linkuse as main transcript	c.1714C>T	p.Pro572Ser	missense_variant	2/6	ENST00000458448.6	NP_001155000.1	A4D1F6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRD1	ENST00000458448.6 linkuse as main transcript	c.1714C>T	p.Pro572Ser	missense_variant	2/6	5	NM_001161528.2	ENSP00000405987.1	A4D1F6-1
ENSG00000289027	ENST00000692281.1 linkuse as main transcript	c.2026-31617C>T		intron_variant				ENSP00000510568.1	A0A8I5KWQ7
ENSG00000285953	ENST00000458493.6 linkuse as main transcript	c.2026-4286C>T		intron_variant		4		ENSP00000396352.2	C9JD81

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000148

AC:

AN:

135548

Hom.:

AF XY:

0.00

AC XY:

AN XY:

72354

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000582

AC:

AN:

1375036

Hom.:

Cov.:

AF XY:

0.00000590

AC XY:

AN XY:

677634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000654

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000472

Hom.:

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 24, 2023

The c.1714C>T (p.P572S) alteration is located in exon 1 (coding exon 1) of the LRRD1 gene. This alteration results from a C to T substitution at nucleotide position 1714, causing the proline (P) at amino acid position 572 to be replaced by a serine (S). 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

0.59

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.1

D;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;D

Vest4

0.39

MutPred

0.65

Loss of ubiquitination at K567 (P = 0.1278);Loss of ubiquitination at K567 (P = 0.1278);

MVP

0.26

ClinPred

0.87

GERP RS

5.4

Varity_R

0.76

gMVP

0.37

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over