7-6402168-G-C

Variant names:

• chr7-6402168-G-C
• rs836551
• NM_006908.5:c.448+141G>C

Variant summary

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

The NM_006908.5(RAC1):​c.448+141G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,441,354 control chromosomes in the GnomAD database, including 203,223 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 0.58 (27284 hom., cov: 30)
  • Exomes 𝑓: 0.51 (175939 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 15 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):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 48

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006908.5. 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
	RAC1	NM_006908.5	MANE Select	c.448+141G>C		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.505+141G>C		intron	N/A	NP_061485.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.448+141G>C		intron	N/A	ENSP00000258737.7
	RAC1	ENST00000356142.4	TSL:1	c.505+141G>C		intron	N/A	ENSP00000348461.4
	RAC1	ENST00000488373.5	TSL:1	n.679+141G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88747 AN: 151772 Hom.: 27234 Cov.: 30

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.512 AC: 660846 AN: 1289464 Hom.: 175939 Cov.: 20 AF XY: 0.513 AC XY: 326287 AN XY: 636294

African (AFR) AF: 0.742 AC: 21484 AN: 28962

American (AMR) AF: 0.691 AC: 21372 AN: 30942

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 7488 AN: 19898

East Asian (EAS) AF: 0.907 AC: 34841 AN: 38412

South Asian (SAS) AF: 0.619 AC: 42822 AN: 69154

European-Finnish (FIN) AF: 0.534 AC: 23358 AN: 43712

Middle Eastern (MID) AF: 0.447 AC: 2205 AN: 4928

European-Non Finnish (NFE) AF: 0.478 AC: 477944 AN: 999600

Other (OTH) AF: 0.545 AC: 29332 AN: 53856

GnomAD4 genome AF: 0.585 AC: 88854 AN: 151890 Hom.: 27284 Cov.: 30 AF XY: 0.592 AC XY: 43937 AN XY: 74212

African (AFR) AF: 0.733 AC: 30353 AN: 41406

American (AMR) AF: 0.632 AC: 9641 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4680 AN: 5146

South Asian (SAS) AF: 0.638 AC: 3071 AN: 4814

European-Finnish (FIN) AF: 0.545 AC: 5751 AN: 10550

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32316 AN: 67934

Other (OTH) AF: 0.561 AC: 1184 AN: 2112

Alfa AF: 0.407 Hom.: 1092

Bravo AF: 0.600

Asia WGS AF: 0.811 AC: 2818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.80
PhyloP100		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs836551; hg19: chr7-6441799; COSMIC: COSV107421692;