rs845930

Variant names:

• chr21-31347809-A-C
• rs845930
• ENST00000653041.1:n.74A>C

Your query was ambiguous. Multiple possible variants found:

• chr21-31347809-A-C
• chr21-31347809-A-G

Variant summary

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

The ENST00000653041.1(ENSG00000286643):​n.74A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 149,240 control chromosomes in the GnomAD database, including 32,959 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 0.67 (32959 hom., cov: 32)
• Consequence: ENSG00000286643 ENST00000653041.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 2 publications found

Genes affected

ENSG00000286643 (HGNC:):

TIAM1 (HGNC:11805): (TIAM Rac1 associated GEF 1) This gene encodes a RAC1-specific guanine nucleotide exchange factor (GEF). GEFs mediate the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP). The binding of GTP induces a conformational change in RAC1 that allows downstream effectors to bind and transduce a signal. This gene thus regulates RAC1 signaling pathways that affect cell shape, migration, adhesion, growth, survival, and polarity, as well as influencing actin cytoskeletal formation, endocytosis, and membrane trafficking. This gene thus plays an important role in cell invasion, metastasis, and carcinogenesis. In addition to RAC1, the encoded protein activates additional Rho-like GTPases such as CDC42, RAC2, RAC3 and RHOA. This gene encodes multiple protein isoforms that experience a diverse array of intramolecular, protein-protein, and phosphorylation interactions as well as phosphoinositide binding. Both the longer and shorter isoforms have C-terminal Dbl homology (DH) and pleckstrin homology (PH) domains while only the longer isoforms of this gene have the N-terminal myristoylation site and the downstream N-terminal PH domain, ras-binding domain (RBD), and PSD-95/DlgA/ZO-1 (PDZ) domain. [provided by RefSeq, Jul 2017]

TIAM1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with language delay and seizures

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIAM1	NM_001353688.1	c.-653-8387T>G		intron_variant	Intron 2 of 29		NP_001340617.1
TIAM1	NM_001353689.1	c.-368-8387T>G		intron_variant	Intron 2 of 28		NP_001340618.1
TIAM1	NM_001353690.1	c.-368-8387T>G		intron_variant	Intron 1 of 27		NP_001340619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286643	ENST00000653041.1	n.74A>C		non_coding_transcript_exon_variant	Exon 1 of 3
TIAM1	ENST00000286827.7	c.-368-8387T>G		intron_variant	Intron 2 of 28	5		ENSP00000286827.3
TIAM1	ENST00000469412.5	n.113-8387T>G		intron_variant	Intron 2 of 8	2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 99599 AN: 149120 Hom.: 32928 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.668 AC: 99677 AN: 149240 Hom.: 32959 Cov.: 32 AF XY: 0.665 AC XY: 48540 AN XY: 72980

African (AFR) AF: 0.763 AC: 29773 AN: 39004

American (AMR) AF: 0.576 AC: 8698 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2566 AN: 3464

East Asian (EAS) AF: 0.553 AC: 2850 AN: 5150

South Asian (SAS) AF: 0.739 AC: 3543 AN: 4796

European-Finnish (FIN) AF: 0.604 AC: 6369 AN: 10544

Middle Eastern (MID) AF: 0.792 AC: 228 AN: 288

European-Non Finnish (NFE) AF: 0.642 AC: 43567 AN: 67904

Other (OTH) AF: 0.678 AC: 1410 AN: 2080

Alfa AF: 0.725 Hom.: 12275

Bravo AF: 0.694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.14
PhyloP100		0.49
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: rs845930; hg19: chr21-32720124;