1-74041209-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001105659.2(LRRIQ3):c.1718+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000485 in 1,553,716 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: LRRIQ3 NM_001105659.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00002147
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-74041209-C-T is Benign according to our data. Variant chr1-74041209-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 716045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2	c.1718+4G>A		splice_donor_region_variant, intron_variant		ENST00000354431.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1718+4G>A		splice_donor_region_variant, intron_variant		5	NM_001105659.2	P2
LRRIQ3	ENST00000395089.5	c.1718+4G>A		splice_donor_region_variant, intron_variant		5		P2
LRRIQ3	ENST00000417067.5	c.131-14240G>A		intron_variant		2
LRRIQ3	ENST00000415760.5	c.*2703+482G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152022 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00949

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000657 AC: 145 AN: 220736 Hom.: 2 AF XY: 0.000575 AC XY: 69 AN XY: 119918

Gnomad AFR exome AF: 0.00887

Gnomad AMR exome AF: 0.000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000409

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.000386

GnomAD4 exome AF: 0.000238 AC: 334 AN: 1401576 Hom.: 1 Cov.: 29 AF XY: 0.000202 AC XY: 141 AN XY: 696910

Gnomad4 AFR exome AF: 0.00862

Gnomad4 AMR exome AF: 0.000248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000176

Gnomad4 OTH exome AF: 0.000657

GnomAD4 genome AF: 0.00275 AC: 419 AN: 152140 Hom.: 1 Cov.: 32 AF XY: 0.00258 AC XY: 192 AN XY: 74378

Gnomad4 AFR AF: 0.00951

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00138 Hom.: 2

Bravo AF: 0.00321

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	0.18
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.064
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: rs181505910; hg19: chr1-74506893; COSMIC: COSV63051239;