NM_006908.5:c.12C>T

Variant names:

• chr7-6374747-C-T
• rs1322357597
• NM_006908.5:c.12C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006908.5(RAC1):​c.12C>T​(p.Ile4Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAC1 NM_006908.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 1 publications found

Genes affected

RAC1 (HGNC:9801): (Rac family small GTPase 1) The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

RAC1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 48

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Illumina, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.812 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.12C>T	p.Ile4Ile	synonymous_variant	Exon 1 of 6	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.12C>T	p.Ile4Ile	synonymous_variant	Exon 1 of 7		NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.12C>T	p.Ile4Ile	synonymous_variant	Exon 1 of 6	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1000260 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 480736

African (AFR) AF: 0.00 AC: 0 AN: 19110

American (AMR) AF: 0.00 AC: 0 AN: 7538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10702

East Asian (EAS) AF: 0.00 AC: 0 AN: 14764

South Asian (SAS) AF: 0.00 AC: 0 AN: 27064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 860174

Other (OTH) AF: 0.00 AC: 0 AN: 35908

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		0.81
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs1322357597; hg19: chr7-6414378;