3-13046812-A-G

Position:

• chr3-13046812-A-G

Variant summary

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

The NM_001134382.3(IQSEC1):​c.23+26180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,650 control chromosomes in the GnomAD database, including 11,324 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 0.37 (11324 hom., cov: 32)
• Consequence: IQSEC1 NM_001134382.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

Genes affected

IQSEC1 (HGNC:29112): (IQ motif and Sec7 domain ArfGEF 1) Predicted to enable protein kinase binding activity. Predicted to be involved in several processes, including positive regulation of focal adhesion disassembly; positive regulation of keratinocyte migration; and regulation of postsynaptic neurotransmitter receptor internalization. Located in nucleolus. Implicated in intellectual developmental disorder with short stature and behavioral abnormalities. [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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC1	NM_001134382.3	c.23+26180T>C		intron_variant		ENST00000613206.2	NP_001127854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC1	ENST00000613206.2	c.23+26180T>C		intron_variant		2	NM_001134382.3	ENSP00000480301
IQSEC1	ENST00000648114.1	c.347+666T>C		intron_variant				ENSP00000497029	A2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56051 AN: 151530 Hom.: 11306 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.370 AC: 56089 AN: 151650 Hom.: 11324 Cov.: 32 AF XY: 0.375 AC XY: 27794 AN XY: 74068

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.375

Alfa AF: 0.403 Hom.: 2190

Bravo AF: 0.380

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.79
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs360902; hg19: chr3-13088312;