chr6-154914505-A-G

Variant names:

• chr6-154914505-A-G
• rs9371835
• ENST00000461783.7:c.-299-29611A>G

Variant summary

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

The ENST00000461783.7(TIAM2):​c.-299-29611A>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 152,102 control chromosomes in the GnomAD database, including 13,097 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 (13097 hom., cov: 31)
• Consequence: TIAM2 ENST00000461783.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 1 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 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.-299-29611A>G		intron_variant	Intron 2 of 28	2		ENSP00000437188.2
TIAM2	ENST00000535064.1	n.327-29611A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62861 AN: 151984 Hom.: 13089 Cov.: 31

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.414 AC: 62896 AN: 152102 Hom.: 13097 Cov.: 31 AF XY: 0.412 AC XY: 30600 AN XY: 74354

African (AFR) AF: 0.464 AC: 19226 AN: 41474

American (AMR) AF: 0.361 AC: 5512 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1239 AN: 3472

East Asian (EAS) AF: 0.498 AC: 2576 AN: 5174

South Asian (SAS) AF: 0.318 AC: 1536 AN: 4828

European-Finnish (FIN) AF: 0.428 AC: 4523 AN: 10572

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27057 AN: 67982

Other (OTH) AF: 0.401 AC: 845 AN: 2108

Alfa AF: 0.399 Hom.: 14795

Bravo AF: 0.415

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-1.6
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: rs9371835; hg19: chr6-155235639;