rs10951982

Variant names:

• chr7-6382925-G-A
• rs10951982
• NM_006908.5:c.36-4287G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-6382925-G-A
• chr7-6382925-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.36-4287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,140 control chromosomes in the GnomAD database, including 2,984 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 0.18 (2984 hom., cov: 33)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 28 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.36-4287G>A		intron_variant	Intron 1 of 5	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.36-4287G>A		intron_variant	Intron 1 of 6		NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.36-4287G>A		intron_variant	Intron 1 of 5	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27526 AN: 152022 Hom.: 2983 Cov.: 33

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.181 AC: 27530 AN: 152140 Hom.: 2984 Cov.: 33 AF XY: 0.181 AC XY: 13424 AN XY: 74368

African (AFR) AF: 0.0703 AC: 2920 AN: 41512

American (AMR) AF: 0.159 AC: 2433 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1204 AN: 5172

South Asian (SAS) AF: 0.159 AC: 765 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2919 AN: 10576

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16452 AN: 67986

Other (OTH) AF: 0.170 AC: 359 AN: 2112

Alfa AF: 0.212 Hom.: 5849

Bravo AF: 0.172

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.72
PhyloP100		-0.32
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: rs10951982; hg19: chr7-6422556;