NM_001145304.2:c.3178-1874T>G

Variant names:

• chr19-18259980-A-C
• rs73003205
• NM_001145304.2:c.3178-1874T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145304.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCN	NM_001145304.2	MANE Select	c.3178-1874T>G		intron	N/A	NP_001138776.1
	IQCN	NM_025249.4		c.2617-1874T>G		intron	N/A	NP_079525.1
	IQCN	NM_001145305.2		c.2479-1874T>G		intron	N/A	NP_001138777.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCN	ENST00000392413.5	TSL:1 MANE Select	c.3178-1874T>G		intron	N/A	ENSP00000376213.2
	IQCN	ENST00000600328.7	TSL:1	c.2617-1874T>G		intron	N/A	ENSP00000470780.1
	IQCN	ENST00000865016.1		c.2617-1874T>G		intron	N/A	ENSP00000535075.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.185 AC: 24 AN: 130

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0500 AC: 1 AN: 20

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0205 AC: 851 AN: 41594

American (AMR) AF: 0.0611 AC: 935 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.0778 AC: 376 AN: 4834

European-Finnish (FIN) AF: 0.188 AC: 1995 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9043 AN: 68024

Other (OTH) AF: 0.0858 AC: 181 AN: 2110

Alfa AF: 0.112 Hom.: 781

Bravo AF: 0.0784

Asia WGS AF: 0.0300 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.034
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: rs73003205; hg19: chr19-18370790;