chr7-6396270-G-A

Variant names:

• chr7-6396270-G-A
• rs12536544
• NM_006908.5:c.226-3856G>A

Variant summary

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

The NM_006908.5(RAC1):​c.226-3856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,028 control chromosomes in the GnomAD database, including 5,623 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 0.24 (5623 hom., cov: 31)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 16 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: 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 = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.226-3856G>A		intron_variant	Intron 3 of 5	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.226-2392G>A		intron_variant	Intron 3 of 6		NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.226-3856G>A		intron_variant	Intron 3 of 5	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36856 AN: 151910 Hom.: 5619 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.242 AC: 36864 AN: 152028 Hom.: 5623 Cov.: 31 AF XY: 0.251 AC XY: 18674 AN XY: 74322

African (AFR) AF: 0.110 AC: 4568 AN: 41498

American (AMR) AF: 0.259 AC: 3949 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3472

East Asian (EAS) AF: 0.739 AC: 3814 AN: 5162

South Asian (SAS) AF: 0.356 AC: 1710 AN: 4806

European-Finnish (FIN) AF: 0.362 AC: 3832 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17800 AN: 67936

Other (OTH) AF: 0.235 AC: 495 AN: 2108

Alfa AF: 0.264 Hom.: 2127

Bravo AF: 0.230

Asia WGS AF: 0.551 AC: 1911 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	0.065
DANN	Benign	0.75
PhyloP100		-1.3
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: rs12536544; hg19: chr7-6435901;