rs9384245

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

SCAF8 (HGNC:20959): (SR-related CTD associated factor 8) Enables RNA binding activity and RNA polymerase II C-terminal domain phosphoserine binding activity. Involved in negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled and positive regulation of DNA-templated transcription, elongation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000461783.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAM2	ENST00000461783.7	TSL:2	c.-561+5585T>C		intron	N/A	ENSP00000437188.2	Q8IVF5-1
	SCAF8	ENST00000899496.1		c.*15-2243T>C		intron	N/A	ENSP00000569555.1
	TIAM2	ENST00000460692.2	TSL:2	n.55+5585T>C		intron	N/A

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

African (AFR) AF: 0.442 AC: 18321 AN: 41442

American (AMR) AF: 0.481 AC: 7347 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1905 AN: 3470

East Asian (EAS) AF: 0.0974 AC: 503 AN: 5164

South Asian (SAS) AF: 0.393 AC: 1887 AN: 4806

European-Finnish (FIN) AF: 0.612 AC: 6466 AN: 10564

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39242 AN: 67960

Other (OTH) AF: 0.501 AC: 1058 AN: 2110

Alfa AF: 0.548 Hom.: 18213

Bravo AF: 0.496

Asia WGS AF: 0.284 AC: 991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.41
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: rs9384245; hg19: chr6-155160128; COSMIC: COSV65790932; COSMIC: COSV65790932;