rs9384245

Variant names:

• chr6-154838994-T-C
• rs9384245
• ENST00000461783.7:c.-561+5585T>C

Variant summary

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

The ENST00000461783.7(TIAM2):​c.-561+5585T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,986 control chromosomes in the GnomAD database, including 20,511 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 0.51 (20511 hom., cov: 32)
• Consequence: TIAM2 ENST00000461783.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

Genes affected

TIAM2 (HGNC:11806): (TIAM Rac1 associated GEF 2) This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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 = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIAM2	ENST00000461783.7	c.-561+5585T>C		intron_variant	Intron 1 of 28	2		ENSP00000437188.2
TIAM2	ENST00000460692.2	n.55+5585T>C		intron_variant	Intron 1 of 1	2
TIAM2	ENST00000535064.1	n.65+5585T>C		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77344 AN: 151866 Hom.: 20496 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.509 AC: 77393 AN: 151986 Hom.: 20511 Cov.: 32 AF XY: 0.508 AC XY: 37739 AN XY: 74288

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.0974

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.501

Alfa AF: 0.549 Hom.: 15325

Bravo AF: 0.496

Asia WGS AF: 0.284 AC: 991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.56

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: rs9384245; hg19: chr6-155160128; COSMIC: COSV65790932; COSMIC: COSV65790932;