1-74041209-C-T

Variant names:

• chr1-74041209-C-T
• rs181505910
• NM_001105659.2:c.1718+4G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001105659.2(LRRIQ3):​c.1718+4G>A variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.00002147
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.1718+4G>A		splice_region_variant, intron_variant	Intron 7 of 7	ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.1718+4G>A		splice_region_variant, intron_variant	Intron 7 of 7	5	NM_001105659.2	ENSP00000346414.4
LRRIQ3	ENST00000395089.5	c.1718+4G>A		splice_region_variant, intron_variant	Intron 6 of 6	5		ENSP00000378524.1
LRRIQ3	ENST00000417067.5	c.131-14240G>A		intron_variant	Intron 1 of 1	2		ENSP00000390376.1
LRRIQ3	ENST00000415760.5	n.*2703+482G>A		intron_variant	Intron 9 of 9	2		ENSP00000415319.1

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

GnomAD2 exomes AF: 0.000657 AC: 145 AN: 220736 AF XY: 0.000575

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 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

African (AFR) AF: 0.00862 AC: 265 AN: 30750

American (AMR) AF: 0.000248 AC: 9 AN: 36292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24180

East Asian (EAS) AF: 0.00 AC: 0 AN: 39214

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 77956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52270

Middle Eastern (MID) AF: 0.000488 AC: 2 AN: 4100

European-Non Finnish (NFE) AF: 0.0000176 AC: 19 AN: 1078950

Other (OTH) AF: 0.000657 AC: 38 AN: 57864

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

African (AFR) AF: 0.00951 AC: 395 AN: 41526

American (AMR) AF: 0.00144 AC: 22 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.18
DANN	Benign	0.53
PhyloP100		-1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs181505910; hg19: chr1-74506893; COSMIC: COSV63051239;