rs73003205

Positions:

• chr19-18259980-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145304.2(IQCN):​c.3178-1874T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,500 control chromosomes in the GnomAD database, including 846 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 0.091 (841 hom., cov: 34)
  • Exomes 𝑓: 0.17 (5 hom.)
• Consequence: IQCN NM_001145304.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

Genes affected

IQCN (HGNC:29350): (IQ motif containing N) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCN	NM_001145304.2	c.3178-1874T>G		intron_variant		ENST00000392413.5	NP_001138776.1
IQCN	NM_001145305.2	c.2479-1874T>G		intron_variant			NP_001138777.1
IQCN	NM_025249.4	c.2617-1874T>G		intron_variant			NP_079525.1
IQCN	XM_005260084.2	c.3178-1874T>G		intron_variant			XP_005260141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCN	ENST00000392413.5	c.3178-1874T>G		intron_variant		1	NM_001145304.2	ENSP00000376213	A2
IQCN	ENST00000600328.7	c.2617-1874T>G		intron_variant		1		ENSP00000470780	P2
IQCN	ENST00000600359.7	c.2479-1874T>G		intron_variant		2		ENSP00000472912	A2
IQCN	ENST00000599638.2	n.2639T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13921 AN: 152232 Hom.: 842 Cov.: 34

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0872

GnomAD4 exome AF: 0.167 AC: 25 AN: 150 Hom.: 5 Cov.: 0 AF XY: 0.250 AC XY: 21 AN XY: 84

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.0500

GnomAD4 genome AF: 0.0914 AC: 13918 AN: 152350 Hom.: 841 Cov.: 34 AF XY: 0.0925 AC XY: 6894 AN XY: 74502

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0611

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.125 Hom.: 367

Bravo AF: 0.0784

Asia WGS AF: 0.0300 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs73003205; hg19: chr19-18370790;