7-6403377-T-G

Variant names:

• chr7-6403377-T-G
• rs6951997
• NM_006908.5:c.*931T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.74).
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2975 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006908.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	NM_006908.5	MANE Select	c.*931T>G		3_prime_UTR	Exon 6 of 6	NP_008839.2
	RAC1	NM_018890.4		c.*931T>G		3_prime_UTR	Exon 7 of 7	NP_061485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.*931T>G		3_prime_UTR	Exon 6 of 6	ENSP00000258737.7
	RAC1	ENST00000704003.1		n.*1463T>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000515616.1
	RAC1	ENST00000704003.1		n.*1463T>G		3_prime_UTR	Exon 7 of 7	ENSP00000515616.1

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

African (AFR) AF: 0.0450 AC: 120 AN: 2666

American (AMR) AF: 0.00854 AC: 15 AN: 1756

Ashkenazi Jewish (ASJ) AF: 0.00131 AC: 5 AN: 3822

East Asian (EAS) AF: 0.00702 AC: 62 AN: 8834

South Asian (SAS) AF: 0.0227 AC: 12 AN: 528

European-Finnish (FIN) AF: 0.0107 AC: 5 AN: 468

Middle Eastern (MID) AF: 0.00824 AC: 3 AN: 364

European-Non Finnish (NFE) AF: 0.0103 AC: 378 AN: 36626

Other (OTH) AF: 0.0148 AC: 73 AN: 4928

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

African (AFR) AF: 0.0438 AC: 1820 AN: 41540

American (AMR) AF: 0.00830 AC: 127 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5192

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4830

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00942 AC: 641 AN: 68034

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.0198 Hom.: 6

Bravo AF: 0.0199

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.0
DANN	Benign	0.72
PhyloP100		0.81
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: rs6951997; hg19: chr7-6443008;