Variant 7-92163571-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001161528.2(LRRD1):c.1632A>C(p.Gln544His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,531,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

LRRD1
NM_001161528.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

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:

CYP51A1-AS1 (HGNC:50694): (CYP51A1 antisense RNA 1)

CYP51A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0817132).

BS2

High AC in GnomAdExome4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRD1	NM_001161528.2 linkuse as main transcript	c.1632A>C	p.Gln544His	missense_variant	2/6	ENST00000458448.6	NP_001155000.1
CYP51A1-AS1	NR_122109.1 linkuse as main transcript	n.1039-1409T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRD1	ENST00000458448.6 linkuse as main transcript	c.1632A>C	p.Gln544His	missense_variant	2/6	5	NM_001161528.2	ENSP00000405987	P1	A4D1F6-1
LRRD1	ENST00000343318.9 linkuse as main transcript	c.-30-4368A>C		intron_variant		1		ENSP00000339642		A4D1F6-2
CYP51A1-AS1	ENST00000453068.1 linkuse as main transcript	n.998-1409T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000217

AC:

AN:

138374

Hom.:

AF XY:

0.0000407

AC XY:

AN XY:

73776

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:

0.0000543

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000638

AC:

AN:

1379480

Hom.:

Cov.:

AF XY:

0.0000662

AC XY:

AN XY:

680270

show subpopulations

Gnomad4 AFR exome

AF:

0.0000332

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:

0.0000792

Gnomad4 OTH exome

AF:

0.0000351

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000415

AC:

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

Jul 09, 2021

The c.1632A>C (p.Q544H) alteration is located in exon 1 (coding exon 1) of the LRRD1 gene. This alteration results from a A to C substitution at nucleotide position 1632, causing the glutamine (Q) at amino acid position 544 to be replaced by a histidine (H). 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

Benign

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.57

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.051

Sift

Benign

0.080

T;T

Sift4G

Benign

0.081

T;T

Polyphen

0.015

B;B

Vest4

0.086

MutPred

0.27

Gain of methylation at K547 (P = 0.1344);Gain of methylation at K547 (P = 0.1344);

MVP

0.16

ClinPred

0.088

GERP RS

3.0

Varity_R

0.14

gMVP

0.21

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