6-155206923-T-C

Variant names:

• chr6-155206923-T-C
• rs7741028
• NM_012454.4:c.3065-4281T>C

Variant summary

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

The NM_012454.4(TIAM2):​c.3065-4281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,274 control chromosomes in the GnomAD database, including 65,403 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 0.93 (65403 hom., cov: 33)
• Consequence: TIAM2 NM_012454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.69
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIAM2	NM_012454.4	c.3065-4281T>C		intron_variant	Intron 14 of 26	ENST00000682666.1	NP_036586.3
TIAM2	NM_001384546.1	c.3065-4281T>C		intron_variant	Intron 14 of 26		NP_001371475.1
TIAM2	NM_001384547.1	c.3065-4281T>C		intron_variant	Intron 13 of 25		NP_001371476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIAM2	ENST00000682666.1	c.3065-4281T>C		intron_variant	Intron 14 of 26		NM_012454.4	ENSP00000507157.1

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140849 AN: 152156 Hom.: 65343 Cov.: 33

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.926 AC: 140968 AN: 152274 Hom.: 65403 Cov.: 33 AF XY: 0.927 AC XY: 69013 AN XY: 74464

African (AFR) AF: 0.980 AC: 40697 AN: 41548

American (AMR) AF: 0.922 AC: 14106 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3282 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5184

South Asian (SAS) AF: 0.951 AC: 4589 AN: 4826

European-Finnish (FIN) AF: 0.897 AC: 9504 AN: 10600

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60608 AN: 68028

Other (OTH) AF: 0.918 AC: 1938 AN: 2112

Alfa AF: 0.903 Hom.: 53026

Bravo AF: 0.930

Asia WGS AF: 0.972 AC: 3378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.38
PhyloP100		-4.7
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: rs7741028; hg19: chr6-155528057;