1-74077243-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105659.2(LRRIQ3):c.868-2453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 150,910 control chromosomes in the GnomAD database, including 17,894 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17894 hom., cov: 32)
• Consequence: LRRIQ3 NM_001105659.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2	c.868-2453A>G		intron_variant		ENST00000354431.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.868-2453A>G		intron_variant		5	NM_001105659.2	P2
LRRIQ3	ENST00000395089.5	c.868-2453A>G		intron_variant		5		P2
LRRIQ3	ENST00000415760.5	c.*2330+1412A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 69911 AN: 150804 Hom.: 17893 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 69922 AN: 150910 Hom.: 17894 Cov.: 32 AF XY: 0.469 AC XY: 34530 AN XY: 73670

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.464

Alfa AF: 0.469 Hom.: 2567

Bravo AF: 0.450

Asia WGS AF: 0.677 AC: 2355 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.9
Dann	Benign	0.57

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

Other links and lift over

dbSNP: rs1483795; hg19: chr1-74542927;