rs12528887

Variant names:

• chr6-155066044-G-A
• rs12528887
• NM_012454.4:c.-208-24245G>A

Variant summary

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

The NM_012454.4(TIAM2):​c.-208-24245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,934 control chromosomes in the GnomAD database, including 10,528 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 0.36 (10528 hom., cov: 31)
• Consequence: TIAM2 NM_012454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIAM2	NM_012454.4	c.-208-24245G>A		intron_variant	Intron 1 of 26	ENST00000682666.1	NP_036586.3
TIAM2	NM_001384546.1	c.-208-24245G>A		intron_variant	Intron 1 of 26		NP_001371475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIAM2	ENST00000682666.1	c.-208-24245G>A		intron_variant	Intron 1 of 26		NM_012454.4	ENSP00000507157.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54289 AN: 151816 Hom.: 10528 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.357 AC: 54295 AN: 151934 Hom.: 10528 Cov.: 31 AF XY: 0.354 AC XY: 26312 AN XY: 74252

African (AFR) AF: 0.208 AC: 8623 AN: 41454

American (AMR) AF: 0.312 AC: 4766 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3466

East Asian (EAS) AF: 0.356 AC: 1831 AN: 5148

South Asian (SAS) AF: 0.438 AC: 2109 AN: 4816

European-Finnish (FIN) AF: 0.383 AC: 4037 AN: 10534

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30211 AN: 67936

Other (OTH) AF: 0.380 AC: 801 AN: 2106

Alfa AF: 0.370 Hom.: 2010

Bravo AF: 0.343

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.82
PhyloP100		-0.34
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: rs12528887; hg19: chr6-155387178;