7-92159178-G-C

Position:

• chr7-92159178-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001384932.1(LRRD1):​c.-5C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,369,008 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: 31)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: LRRD1 NM_001384932.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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]

ENSG00000285953 (HGNC:):

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

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.106312335).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRD1	NM_001161528.2	c.1943C>G	p.Ser648Cys	missense_variant	3/6	ENST00000458448.6	NP_001155000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRD1	ENST00000458448.6	c.1943C>G	p.Ser648Cys	missense_variant	3/6	5	NM_001161528.2	ENSP00000405987.1
ENSG00000285953	ENST00000458493.6	c.2051C>G	p.Ser684Cys	missense_variant	17/20	4		ENSP00000396352.2
ENSG00000289027	ENST00000692281.1	c.2026-27306C>G		intron_variant				ENSP00000510568.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000438 AC: 6 AN: 1369008 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 674630

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: 0.00000468

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 31

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

May 26, 2022

The c.1943C>G (p.S648C) alteration is located in exon 2 (coding exon 2) of the LRRD1 gene. This alteration results from a C to G substitution at nucleotide position 1943, causing the serine (S) at amino acid position 648 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	0.067
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.0061	T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.014
Sift	Benign	0.17	T;T
Sift4G	Uncertain	0.039	D;D
Polyphen		0.030	B;B
Vest4		0.13
MutPred		0.43		Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);
MVP		0.12
ClinPred		0.20	T
GERP RS		2.9
Varity_R		0.10
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-91788492;