rs2011738

Positions:

• chr12-110822-A-G
• chr12-110822-A-T

Variant summary

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

The NM_001170738.2(IQSEC3):​c.623+11608A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,890 control chromosomes in the GnomAD database, including 13,927 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 0.41 (13927 hom., cov: 31)
• Consequence: IQSEC3 NM_001170738.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

Genes affected

IQSEC3 (HGNC:29193): (IQ motif and Sec7 domain ArfGEF 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of small GTPase mediated signal transduction. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256948 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC3	NM_001170738.2	c.623+11608A>G		intron_variant		ENST00000538872.6	NP_001164209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC3	ENST00000538872.6	c.623+11608A>G		intron_variant		5	NM_001170738.2	ENSP00000437554.1
IQSEC3	ENST00000382841.2	c.-7+11608A>G		intron_variant		2		ENSP00000372292.2
ENSG00000256948	ENST00000540226.1	n.232+797T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62845 AN: 151774 Hom.: 13918 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.414 AC: 62896 AN: 151890 Hom.: 13927 Cov.: 31 AF XY: 0.419 AC XY: 31122 AN XY: 74244

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.431

Alfa AF: 0.384 Hom.: 10073

Bravo AF: 0.430

Asia WGS AF: 0.669 AC: 2326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.63

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: rs2011738; hg19: chr12-219988;