chr1-74044121-C-T

Variant names:

• chr1-74044121-C-T
• rs6676622
• NM_001105659.2:c.998-2188G>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.998-2188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,952 control chromosomes in the GnomAD database, including 18,708 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 0.48 (18708 hom., cov: 32)
• Consequence: LRRIQ3 NM_001105659.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRIQ3	NM_001105659.2	c.998-2188G>A		intron_variant	Intron 6 of 7	ENST00000354431.9	NP_001099129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRIQ3	ENST00000354431.9	c.998-2188G>A		intron_variant	Intron 6 of 7	5	NM_001105659.2	ENSP00000346414.4
LRRIQ3	ENST00000395089.5	c.998-2188G>A		intron_variant	Intron 5 of 6	5		ENSP00000378524.1
LRRIQ3	ENST00000417067.5	c.131-17152G>A		intron_variant	Intron 1 of 1	2		ENSP00000390376.1
LRRIQ3	ENST00000415760.5	n.*2461-2188G>A		intron_variant	Intron 8 of 9	2		ENSP00000415319.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72452 AN: 151834 Hom.: 18702 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.477 AC: 72480 AN: 151952 Hom.: 18708 Cov.: 32 AF XY: 0.482 AC XY: 35829 AN XY: 74288

African (AFR) AF: 0.284 AC: 11786 AN: 41442

American (AMR) AF: 0.492 AC: 7503 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2212 AN: 3464

East Asian (EAS) AF: 0.819 AC: 4222 AN: 5158

South Asian (SAS) AF: 0.662 AC: 3187 AN: 4814

European-Finnish (FIN) AF: 0.543 AC: 5733 AN: 10566

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.532 AC: 36115 AN: 67942

Other (OTH) AF: 0.470 AC: 991 AN: 2110

Alfa AF: 0.476 Hom.: 2300

Bravo AF: 0.464

Asia WGS AF: 0.681 AC: 2371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.42
PhyloP100		-0.98
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: rs6676622; hg19: chr1-74509805;