rs374518114

Variant names:

• chr7-102468072-C-G
• rs374518114
• NM_152892.3:c.689C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-102468072-C-G
• chr7-102468072-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152892.3(LRWD1):​c.689C>G​(p.Ala230Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A230T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRWD1 NM_152892.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 0 publications found

Genes affected

LRWD1 (HGNC:21769): (leucine rich repeats and WD repeat domain containing 1) The protein encoded by this gene interacts with components of the origin recognition complex (ORC) and regulates the formation of the prereplicative complex. The encoded protein stabilizes the ORC and therefore aids in DNA replication. This protein is required for the G1/S phase transition of the cell cycle. In addition, the encoded protein binds to trimethylated histone H3 in heterochromatin and recruits the ORC and lysine methyltransferases, which help maintain the repressive heterochromatic state. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048604548).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152892.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRWD1	NM_152892.3	MANE Select	c.689C>G	p.Ala230Gly	missense	Exon 6 of 15	NP_690852.1	Q9UFC0
	LRWD1	NM_001317721.2		c.233C>G	p.Ala78Gly	missense	Exon 6 of 15	NP_001304650.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRWD1	ENST00000292616.10	TSL:1 MANE Select	c.689C>G	p.Ala230Gly	missense	Exon 6 of 15	ENSP00000292616.5	Q9UFC0
	LRWD1	ENST00000896262.1		c.689C>G	p.Ala230Gly	missense	Exon 6 of 16	ENSP00000566321.1
	LRWD1	ENST00000922655.1		c.689C>G	p.Ala230Gly	missense	Exon 6 of 15	ENSP00000592714.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455980 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724542

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.0000224 AC: 1 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111520

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.56
DANN	Benign	0.86
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.7
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.053
Sift	Benign	0.38	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.20		Loss of helix (P = 0.0558)
MVP		0.16
MPC		0.050
ClinPred		0.084	T
GERP RS		-8.3
Varity_R		0.041
gMVP		0.27
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374518114; hg19: chr7-102108519;