chr7-6402168-G-C

Position:

• chr7-6402168-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000348035.9(RAC1):​c.448+141G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,441,354 control chromosomes in the GnomAD database, including 203,223 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 0.58 (27284 hom., cov: 30)
  • Exomes 𝑓: 0.51 (175939 hom.)
• Consequence: RAC1 ENST00000348035.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC1	NM_006908.5	c.448+141G>C		intron_variant		ENST00000348035.9	NP_008839.2
RAC1	NM_018890.4	c.505+141G>C		intron_variant			NP_061485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC1	ENST00000348035.9	c.448+141G>C		intron_variant		1	NM_006908.5	ENSP00000258737	P1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88747 AN: 151772 Hom.: 27234 Cov.: 30

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.512 AC: 660846 AN: 1289464 Hom.: 175939 Cov.: 20 AF XY: 0.513 AC XY: 326287 AN XY: 636294

Gnomad4 AFR exome AF: 0.742

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.907

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.478

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.585 AC: 88854 AN: 151890 Hom.: 27284 Cov.: 30 AF XY: 0.592 AC XY: 43937 AN XY: 74212

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.561

Alfa AF: 0.407 Hom.: 1092

Bravo AF: 0.600

Asia WGS AF: 0.811 AC: 2818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs836551; hg19: chr7-6441799;