rs729358

Variant names:

• chr1-156567307-G-A
• rs729358
• NM_178229.5:c.126-761C>T

Variant summary

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

The NM_178229.5(IQGAP3):​c.126-761C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 152,284 control chromosomes in the GnomAD database, including 70,692 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 0.96 (70692 hom., cov: 32)
• Consequence: IQGAP3 NM_178229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 2 publications found

Genes affected

IQGAP3 (HGNC:20669): (IQ motif containing GTPase activating protein 3) Enables calmodulin binding activity and myosin VI light chain binding activity. Predicted to be involved in regulation of actin cytoskeleton organization. Predicted to act upstream of or within several processes, including intracellular signal transduction; positive regulation of macromolecule metabolic process; and positive regulation of mammary gland epithelial cell proliferation. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQGAP3	NM_178229.5	c.126-761C>T		intron_variant	Intron 2 of 37	ENST00000361170.7	NP_839943.3
IQGAP3	XM_011509198.4	c.141-761C>T		intron_variant	Intron 2 of 37		XP_011507500.1
IQGAP3	XM_047445990.1	c.141-761C>T		intron_variant	Intron 2 of 37		XP_047301946.1
IQGAP3	XM_047445996.1	c.126-761C>T		intron_variant	Intron 2 of 37		XP_047301952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQGAP3	ENST00000361170.7	c.126-761C>T		intron_variant	Intron 2 of 37	1	NM_178229.5	ENSP00000354451.2
IQGAP3	ENST00000491900.1	n.-4-761C>T		intron_variant	Intron 1 of 37	1		ENSP00000436603.1

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146352 AN: 152166 Hom.: 70644 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.980

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

GnomAD4 genome AF: 0.962 AC: 146458 AN: 152284 Hom.: 70692 Cov.: 32 AF XY: 0.962 AC XY: 71623 AN XY: 74464

African (AFR) AF: 0.866 AC: 35942 AN: 41524

American (AMR) AF: 0.989 AC: 15128 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.998 AC: 4818 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68027 AN: 68044

Other (OTH) AF: 0.980 AC: 2070 AN: 2112

Alfa AF: 0.976 Hom.: 9400

Bravo AF: 0.957

Asia WGS AF: 0.994 AC: 3455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-0.18
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: rs729358; hg19: chr1-156537099; COSMIC: COSV63249283;