chr7-92163740-G-C

Position:

• chr7-92163740-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001161528.2(LRRD1):​c.1463C>G​(p.Ser488Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: LRRD1 NM_001161528.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.713

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]

ENSG00000289027 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38593727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRD1	NM_001161528.2	c.1463C>G	p.Ser488Cys	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.1463C>G	p.Ser488Cys	missense_variant	2/6	5	NM_001161528.2	ENSP00000405987.1
ENSG00000289027	ENST00000692281.1	c.2026-31868C>G		intron_variant				ENSP00000510568.1
ENSG00000285953	ENST00000458493.6	c.2026-4537C>G		intron_variant		4		ENSP00000396352.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.1463C>G (p.S488C) alteration is located in exon 1 (coding exon 1) of the LRRD1 gene. This alteration results from a C to G substitution at nucleotide position 1463, causing the serine (S) at amino acid position 488 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.3	M;M
MutationTaster	Benign	0.64	D;D;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		1.0	D;D
Vest4		0.31
MutPred		0.59		Gain of catalytic residue at L489 (P = 0.0245);Gain of catalytic residue at L489 (P = 0.0245);
MVP		0.23
ClinPred		0.78	D
GERP RS		2.2
Varity_R		0.14
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-91793054;