rs765248

Positions:

• chr3-12960431-G-A

Variant summary

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

The NM_001134382.3(IQSEC1):​c.24-18566C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,026 control chromosomes in the GnomAD database, including 11,503 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 (11500 hom., cov: 31)
  • Exomes 𝑓: 0.36 (3 hom.)
• Consequence: IQSEC1 NM_001134382.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC1	NM_001134382.3	c.24-18566C>T		intron_variant		ENST00000613206.2	NP_001127854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC1	ENST00000613206.2	c.24-18566C>T		intron_variant		2	NM_001134382.3	ENSP00000480301

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56495 AN: 151866 Hom.: 11504 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.357 AC: 15 AN: 42 Hom.: 3 Cov.: 0 AF XY: 0.441 AC XY: 15 AN XY: 34

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.372 AC: 56499 AN: 151984 Hom.: 11500 Cov.: 31 AF XY: 0.364 AC XY: 27074 AN XY: 74282

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.429

Alfa AF: 0.444 Hom.: 16247

Bravo AF: 0.374

Asia WGS AF: 0.209 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	13
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs765248; hg19: chr3-13001931;