7-6374447-G-C

Variant names:

• chr7-6374447-G-C
• rs34932801
• ENST00000966157.1:c.-195-94G>C

Variant summary

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

The ENST00000966157.1(RAC1):​c.-195-94G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 158,262 control chromosomes in the GnomAD database, including 1,177 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 0.078 (1105 hom., cov: 32)
  • Exomes 𝑓: 0.070 (72 hom.)
• Consequence: RAC1 ENST00000966157.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 10 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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000966157.1. 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.-289G>C		upstream_gene	N/A	NP_008839.2
	RAC1	NM_018890.4		c.-289G>C		upstream_gene	N/A	NP_061485.1	P63000-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000966157.1		c.-195-94G>C		intron	N/A	ENSP00000636216.1
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.-289G>C		upstream_gene	N/A	ENSP00000258737.7	P63000-1
	RAC1	ENST00000356142.4	TSL:1	c.-289G>C		upstream_gene	N/A	ENSP00000348461.4	P63000-2

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11846 AN: 151490 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0745

GnomAD4 exome AF: 0.0698 AC: 465 AN: 6664 Hom.: 72 AF XY: 0.0639 AC XY: 239 AN XY: 3740

African (AFR) AF: 0.0588 AC: 10 AN: 170

American (AMR) AF: 0.0960 AC: 19 AN: 198

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 11 AN: 218

East Asian (EAS) AF: 0.524 AC: 238 AN: 454

South Asian (SAS) AF: 0.130 AC: 38 AN: 292

European-Finnish (FIN) AF: 0.0681 AC: 26 AN: 382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 30

European-Non Finnish (NFE) AF: 0.0210 AC: 95 AN: 4518

Other (OTH) AF: 0.0697 AC: 28 AN: 402

GnomAD4 genome AF: 0.0784 AC: 11882 AN: 151598 Hom.: 1105 Cov.: 32 AF XY: 0.0879 AC XY: 6512 AN XY: 74094

African (AFR) AF: 0.0872 AC: 3613 AN: 41422

American (AMR) AF: 0.105 AC: 1604 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3468

East Asian (EAS) AF: 0.504 AC: 2563 AN: 5090

South Asian (SAS) AF: 0.205 AC: 987 AN: 4818

European-Finnish (FIN) AF: 0.0920 AC: 959 AN: 10422

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0258 AC: 1754 AN: 67856

Other (OTH) AF: 0.0794 AC: 167 AN: 2102

Alfa AF: 0.0475 Hom.: 44

Bravo AF: 0.0755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		0.12
PromoterAI		-0.019	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34932801; hg19: chr7-6414078;