7-6392059-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006908.5(RAC1):c.225+18C>T 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 1,613,614 control chromosomes in the GnomAD database, including 218,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (26069 hom., cov: 32)
  • Exomes 𝑓: 0.50 (192497 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 7-6392059-C-T is Benign according to our data. Variant chr7-6392059-C-T is described in ClinVar as [Benign]. Clinvar id is 1327930.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-6392059-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.225+18C>T		intron_variant		ENST00000348035.9
RAC1	NM_018890.4	c.225+18C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.225+18C>T		intron_variant		1	NM_006908.5	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86584 AN: 151868 Hom.: 26019 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.540

GnomAD3 exomes AF: 0.562 AC: 141158 AN: 251230 Hom.: 42598 AF XY: 0.551 AC XY: 74788 AN XY: 135808

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.911

Gnomad SAS exome AF: 0.618

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.503 AC: 735385 AN: 1461628 Hom.: 192497 Cov.: 50 AF XY: 0.504 AC XY: 366140 AN XY: 727068

Gnomad4 AFR exome AF: 0.725

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.906

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.570 AC: 86694 AN: 151986 Hom.: 26069 Cov.: 32 AF XY: 0.575 AC XY: 42697 AN XY: 74276

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.546

Alfa AF: 0.518 Hom.: 4602

Bravo AF: 0.590

Asia WGS AF: 0.809 AC: 2812 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 48 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	8.4
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs836478; hg19: chr7-6431690;