rs9478613

Variant names:

• chr6-155103116-T-G
• rs9478613
• NM_012454.4:c.-118+12737T>G

Variant summary

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

The NM_012454.4(TIAM2):​c.-118+12737T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,002 control chromosomes in the GnomAD database, including 19,690 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 0.50 (19690 hom., cov: 31)
• Consequence: TIAM2 NM_012454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIAM2	NM_012454.4	c.-118+12737T>G		intron_variant	Intron 2 of 26	ENST00000682666.1	NP_036586.3
TIAM2	NM_001384546.1	c.-118+12737T>G		intron_variant	Intron 2 of 26		NP_001371475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIAM2	ENST00000682666.1	c.-118+12737T>G		intron_variant	Intron 2 of 26		NM_012454.4	ENSP00000507157.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76213 AN: 151884 Hom.: 19650 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.502 AC: 76296 AN: 152002 Hom.: 19690 Cov.: 31 AF XY: 0.497 AC XY: 36953 AN XY: 74300

African (AFR) AF: 0.590 AC: 24469 AN: 41454

American (AMR) AF: 0.533 AC: 8137 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5170

South Asian (SAS) AF: 0.313 AC: 1510 AN: 4824

European-Finnish (FIN) AF: 0.480 AC: 5066 AN: 10554

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32344 AN: 67958

Other (OTH) AF: 0.516 AC: 1090 AN: 2112

Alfa AF: 0.491 Hom.: 24157

Bravo AF: 0.510

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.6
DANN	Benign	0.70
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: rs9478613; hg19: chr6-155424250;