rs6954996

Variant names:

• chr7-6401627-G-A
• rs6954996
• NM_006908.5:c.289-241G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-6401627-G-A
• chr7-6401627-G-C
• chr7-6401627-G-T

Variant summary

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

The NM_006908.5(RAC1):​c.289-241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0595 in 322,038 control chromosomes in the GnomAD database, including 1,077 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 0.079 (843 hom., cov: 32)
  • Exomes 𝑓: 0.042 (234 hom.)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 5 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: G2P, Orphanet, Ambry Genetics, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 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.289-241G>A		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.346-241G>A		intron	N/A	NP_061485.1	P63000-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.289-241G>A		intron	N/A	ENSP00000258737.7	P63000-1
	RAC1	ENST00000356142.4	TSL:1	c.346-241G>A		intron	N/A	ENSP00000348461.4	P63000-2
	RAC1	ENST00000488373.5	TSL:1	n.520-241G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11988 AN: 152022 Hom.: 843 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0421 AC: 7160 AN: 169896 Hom.: 234 Cov.: 3 AF XY: 0.0422 AC XY: 3640 AN XY: 86184

African (AFR) AF: 0.182 AC: 947 AN: 5210

American (AMR) AF: 0.0284 AC: 152 AN: 5356

Ashkenazi Jewish (ASJ) AF: 0.0459 AC: 299 AN: 6520

East Asian (EAS) AF: 0.0641 AC: 907 AN: 14152

South Asian (SAS) AF: 0.0913 AC: 620 AN: 6790

European-Finnish (FIN) AF: 0.0356 AC: 429 AN: 12064

Middle Eastern (MID) AF: 0.0275 AC: 33 AN: 1198

European-Non Finnish (NFE) AF: 0.0294 AC: 3149 AN: 107216

Other (OTH) AF: 0.0548 AC: 624 AN: 11390

GnomAD4 genome AF: 0.0789 AC: 11998 AN: 152142 Hom.: 843 Cov.: 32 AF XY: 0.0790 AC XY: 5875 AN XY: 74390

African (AFR) AF: 0.184 AC: 7638 AN: 41488

American (AMR) AF: 0.0370 AC: 565 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 163 AN: 3470

East Asian (EAS) AF: 0.0880 AC: 455 AN: 5172

South Asian (SAS) AF: 0.101 AC: 486 AN: 4822

European-Finnish (FIN) AF: 0.0354 AC: 376 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0316 AC: 2145 AN: 67974

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0319 Hom.: 56

Bravo AF: 0.0830

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.65
PhyloP100		-1.1
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)		0.010		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: rs6954996; hg19: chr7-6441258;