1-74198025-G-A

Variant names:

• chr1-74198025-G-A
• rs11806946
• ENST00000463724.1:n.123C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000463724.1(LRRIQ3):​n.123C>T variant causes a non coding transcript exon 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 ENST00000463724.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000463724.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ3	NM_001105659.2	MANE Select	c.-30C>T		5_prime_UTR	Exon 1 of 8	NP_001099129.1
	LRRIQ3	NM_001322315.2		c.-30C>T		5_prime_UTR	Exon 1 of 8	NP_001309244.1
	FPGT	NM_003838.5	MANE Select	c.-254G>A		upstream_gene	N/A	NP_003829.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ3	ENST00000463724.1	TSL:1	n.123C>T		non_coding_transcript_exon	Exon 1 of 2
	LRRIQ3	ENST00000354431.9	TSL:5 MANE Select	c.-30C>T		5_prime_UTR	Exon 1 of 8	ENSP00000346414.4
	LRRIQ3	ENST00000370911.7	TSL:1	c.-30C>T		5_prime_UTR	Exon 1 of 4	ENSP00000359948.3

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

African (AFR) AF: 0.207 AC: 2888 AN: 13928

American (AMR) AF: 0.411 AC: 6464 AN: 15716

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 7213 AN: 13162

East Asian (EAS) AF: 0.692 AC: 20177 AN: 29168

South Asian (SAS) AF: 0.557 AC: 18700 AN: 33550

European-Finnish (FIN) AF: 0.469 AC: 12941 AN: 27602

Middle Eastern (MID) AF: 0.494 AC: 1006 AN: 2038

European-Non Finnish (NFE) AF: 0.473 AC: 169258 AN: 357946

Other (OTH) AF: 0.475 AC: 13123 AN: 27626

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

African (AFR) AF: 0.212 AC: 8805 AN: 41524

American (AMR) AF: 0.425 AC: 6484 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3468

East Asian (EAS) AF: 0.729 AC: 3760 AN: 5156

South Asian (SAS) AF: 0.545 AC: 2629 AN: 4828

European-Finnish (FIN) AF: 0.499 AC: 5280 AN: 10582

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32310 AN: 67968

Other (OTH) AF: 0.407 AC: 859 AN: 2112

Alfa AF: 0.446 Hom.: 39032

Bravo AF: 0.400

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.64
PhyloP100		0.15
PromoterAI		-0.044	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11806946; hg19: chr1-74663709;