1-74198025-G-A

Position:

• chr1-74198025-G-A

Variant summary

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

The NM_001105659.2(LRRIQ3):​c.-30C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 672,832 control chromosomes in the GnomAD database, including 77,197 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 0.41 (14380 hom., cov: 33)
  • Exomes 𝑓: 0.48 (62817 hom.)
• Consequence: LRRIQ3 NM_001105659.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2	c.-30C>T		5_prime_UTR_variant	1/8	ENST00000354431.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.-30C>T		5_prime_UTR_variant	1/8	5	NM_001105659.2	P2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62778 AN: 151980 Hom.: 14387 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.483 AC: 251770 AN: 520736 Hom.: 62817 Cov.: 7 AF XY: 0.487 AC XY: 128968 AN XY: 264652

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.411

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.692

Gnomad4 SAS exome AF: 0.557

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.413 AC: 62773 AN: 152096 Hom.: 14380 Cov.: 33 AF XY: 0.418 AC XY: 31078 AN XY: 74334

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.407

Alfa AF: 0.466 Hom.: 26067

Bravo AF: 0.400

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11806946; hg19: chr1-74663709;