rs6951997

chr7-6403377-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006908.5(RAC1):c.*931T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 212,312 control chromosomes in the GnomAD database, including 73 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 0.020 (66 hom., cov: 33)
  • Exomes 𝑓: 0.011 (7 hom.)
• Consequence: RAC1 NM_006908.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0195 (2975/152320) while in subpopulation AFR AF= 0.0438 (1820/41540). AF 95% confidence interval is 0.0421. There are 66 homozygotes in gnomad4. There are 1465 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2972 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC1	NM_006908.5	c.*931T>G		3_prime_UTR_variant	6/6	ENST00000348035.9
RAC1	NM_018890.4	c.*931T>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC1	ENST00000348035.9	c.*931T>G		3_prime_UTR_variant	6/6	1	NM_006908.5	P1
RAC1	ENST00000704003.1	c.*1463T>G		3_prime_UTR_variant, NMD_transcript_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2972 AN: 152202 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00942

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0112 AC: 673 AN: 59992 Hom.: 7 Cov.: 0 AF XY: 0.0114 AC XY: 318 AN XY: 27792

Gnomad4 AFR exome AF: 0.0450

Gnomad4 AMR exome AF: 0.00854

Gnomad4 ASJ exome AF: 0.00131

Gnomad4 EAS exome AF: 0.00702

Gnomad4 SAS exome AF: 0.0227

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.0195 AC: 2975 AN: 152320 Hom.: 66 Cov.: 33 AF XY: 0.0197 AC XY: 1465 AN XY: 74480

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.00942

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0192 Hom.: 6

Bravo AF: 0.0199

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.0
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs6951997; hg19: chr7-6443008;