chr7-6383715-A-T

Variant names:

• chr7-6383715-A-T
• rs10238136
• NM_006908.5:c.36-3497A>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.36-3497A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 151,342 control chromosomes in the GnomAD database, including 753 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 0.075 (753 hom., cov: 31)
• Consequence: RAC1 NM_006908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC1	NM_006908.5	c.36-3497A>T		intron_variant	Intron 1 of 5	ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.36-3497A>T		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.36-3497A>T		intron_variant	Intron 1 of 5	1	NM_006908.5	ENSP00000258737.7

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 11314 AN: 151226 Hom.: 751 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0471

Gnomad EAS AF: 0.0865

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0606

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

GnomAD4 genome AF: 0.0748 AC: 11324 AN: 151342 Hom.: 753 Cov.: 31 AF XY: 0.0746 AC XY: 5521 AN XY: 74042

African (AFR) AF: 0.171 AC: 7012 AN: 40950

American (AMR) AF: 0.0358 AC: 544 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0471 AC: 163 AN: 3462

East Asian (EAS) AF: 0.0865 AC: 446 AN: 5156

South Asian (SAS) AF: 0.0978 AC: 469 AN: 4796

European-Finnish (FIN) AF: 0.0350 AC: 367 AN: 10500

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

European-Non Finnish (NFE) AF: 0.0317 AC: 2155 AN: 67958

Other (OTH) AF: 0.0599 AC: 126 AN: 2102

Alfa AF: 0.0557 Hom.: 59

Bravo AF: 0.0790

Asia WGS AF: 0.0880 AC: 306 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		2.1
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: rs10238136; hg19: chr7-6423346;