chr1-74041280-T-G

Variant names:

• chr1-74041280-T-G
• rs1011230954
• NM_001105659.2:c.1651A>C

Variant summary

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

The NM_001105659.2(LRRIQ3):​c.1651A>C​(p.Ile551Leu) 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. 16/22 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. I551V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRIQ3 NM_001105659.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 0 publications found

Genes affected

LRRIQ3 (HGNC:28318): (leucine rich repeats and IQ motif containing 3)

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=0.0678522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1651A>C	p.Ile551Leu	missense_variant	Exon 7 of 8	ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1651A>C	p.Ile551Leu	missense_variant	Exon 7 of 8	5	NM_001105659.2	ENSP00000346414.4
LRRIQ3	ENST00000395089.5	c.1651A>C	p.Ile551Leu	missense_variant	Exon 6 of 7	5		ENSP00000378524.1
LRRIQ3	ENST00000417067.5	c.131-14311A>C		intron_variant	Intron 1 of 1	2		ENSP00000390376.1
LRRIQ3	ENST00000415760.5	n.*2703+411A>C		intron_variant	Intron 9 of 9	2		ENSP00000415319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.2
DANN	Benign	0.20
DEOGEN2	Benign	0.0042	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.38	.;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.5	L;L
PhyloP100		-0.16
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.067
Sift	Benign	0.038	D;D
Sift4G	Benign	0.48	T;T
Polyphen		0.28	B;B
Vest4		0.26
MutPred		0.14		Loss of methylation at K553 (P = 0.0719);Loss of methylation at K553 (P = 0.0719);
MVP		0.030
MPC		0.0043
ClinPred		0.078	T
GERP RS		-6.0
Varity_R		0.055
gMVP		0.0081
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1011230954; hg19: chr1-74506964;