rs11806946

Variant names:

• chr1-74198025-G-A
• rs11806946
• NM_001105659.2:c.-30C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-74198025-G-A
• chr1-74198025-G-C

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)

FPGT (HGNC:3825): (fucose-1-phosphate guanylyltransferase) L-fucose is a key sugar in glycoproteins and other complex carbohydrates since it may be involved in many of the functional roles of these macromolecules, such as in cell-cell recognition. The fucosyl donor for these fucosylated oligosaccharides is GDP-beta-L-fucose. There are two alternate pathways for the biosynthesis of GDP-fucose; the major pathway converts GDP-alpha-D-mannose to GDP-beta-L-fucose. The protein encoded by this gene participates in an alternate pathway that is present in certain mammalian tissues, such as liver and kidney, and appears to function as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids. This pathway involves the phosphorylation of L-fucose to form beta-L-fucose-1-phosphate, and then condensation of the beta-L-fucose-1-phosphate with GTP by fucose-1-phosphate guanylyltransferase to form GDP-beta-L-fucose. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream TNNI3 interacting kinase (TNNI3K) gene. [provided by RefSeq, Dec 2010]

FPGT-TNNI3K (HGNC:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.-30C>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000354431.9	NP_001099129.1
FPGT	NM_003838.5	c.-254G>A		upstream_gene_variant		ENST00000370898.9	NP_003829.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.-30C>T		5_prime_UTR_variant	Exon 1 of 8	5	NM_001105659.2	ENSP00000346414.4
FPGT	ENST00000370898.9	c.-254G>A		upstream_gene_variant		1	NM_003838.5	ENSP00000359935.4
FPGT-TNNI3K	ENST00000557284.7	c.-254G>A		upstream_gene_variant		2		ENSP00000450895.3

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;