rs4142948

Variant names:

• chr1-74106667-C-T
• rs4142948
• NM_001105659.2:c.867+2727G>A

Variant summary

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

The NM_001105659.2(LRRIQ3):​c.867+2727G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,658 control chromosomes in the GnomAD database, including 18,250 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 0.47 (18250 hom., cov: 31)
• Consequence: LRRIQ3 NM_001105659.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 5 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105659.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ3	NM_001105659.2	MANE Select	c.867+2727G>A		intron	N/A	NP_001099129.1	A6PVS8-1
	LRRIQ3	NM_001322315.2		c.867+2727G>A		intron	N/A	NP_001309244.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRIQ3	ENST00000354431.9	TSL:5 MANE Select	c.867+2727G>A		intron	N/A	ENSP00000346414.4	A6PVS8-1
	LRRIQ3	ENST00000395089.5	TSL:5	c.867+2727G>A		intron	N/A	ENSP00000378524.1	A6PVS8-1
	LRRIQ3	ENST00000370909.6	TSL:5	c.543+2727G>A		intron	N/A	ENSP00000359946.2	A8MSG4

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70865 AN: 151542 Hom.: 18244 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.467 AC: 70892 AN: 151658 Hom.: 18250 Cov.: 31 AF XY: 0.473 AC XY: 35009 AN XY: 74058

African (AFR) AF: 0.251 AC: 10404 AN: 41382

American (AMR) AF: 0.488 AC: 7394 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4204 AN: 5128

South Asian (SAS) AF: 0.663 AC: 3187 AN: 4806

European-Finnish (FIN) AF: 0.541 AC: 5702 AN: 10532

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36065 AN: 67872

Other (OTH) AF: 0.469 AC: 987 AN: 2106

Alfa AF: 0.469 Hom.: 2264

Bravo AF: 0.454

Asia WGS AF: 0.681 AC: 2367 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.78
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs4142948; hg19: chr1-74572351;