rs4980804

Variant names:

• chr12-152763-T-C
• rs4980804
• NM_001170738.2:c.2154-4262T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-152763-T-C
• chr12-152763-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001170738.2(IQSEC3):​c.2154-4262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,064 control chromosomes in the GnomAD database, including 12,714 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 0.38 (12714 hom., cov: 32)
• Consequence: IQSEC3 NM_001170738.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC3	NM_001170738.2	c.2154-4262T>C		intron_variant	Intron 5 of 13	ENST00000538872.6	NP_001164209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQSEC3	ENST00000538872.6	c.2154-4262T>C		intron_variant	Intron 5 of 13	5	NM_001170738.2	ENSP00000437554.1
IQSEC3	ENST00000382841.2	c.1245-4262T>C		intron_variant	Intron 4 of 12	2		ENSP00000372292.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57697 AN: 151946 Hom.: 12720 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.379 AC: 57702 AN: 152064 Hom.: 12714 Cov.: 32 AF XY: 0.376 AC XY: 27967 AN XY: 74334

African (AFR) AF: 0.152 AC: 6307 AN: 41484

American (AMR) AF: 0.473 AC: 7229 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1740 AN: 5140

South Asian (SAS) AF: 0.344 AC: 1660 AN: 4820

European-Finnish (FIN) AF: 0.382 AC: 4040 AN: 10572

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33940 AN: 67976

Other (OTH) AF: 0.396 AC: 836 AN: 2112

Alfa AF: 0.466 Hom.: 25393

Bravo AF: 0.379

Asia WGS AF: 0.311 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.40
PhyloP100		-2.7
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: rs4980804; hg19: chr12-261929;