7-6387310-C-T

Variant names:

• chr7-6387310-C-T
• rs702483
• NM_006908.5:c.107+27C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018890.4(RAC1):​c.107+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,442,870 control chromosomes in the GnomAD database, including 199,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (29343 hom., cov: 33)
  • Exomes 𝑓: 0.50 (170650 hom.)
• Consequence: RAC1 NM_018890.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.769
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-6387310-C-T is Benign according to our data. Variant chr7-6387310-C-T is described in ClinVar as Benign. ClinVar VariationId is 1327929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018890.4. 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.107+27C>T		intron	N/A	NP_008839.2
	RAC1	NM_018890.4		c.107+27C>T		intron	N/A	NP_061485.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC1	ENST00000348035.9	TSL:1 MANE Select	c.107+27C>T		intron	N/A	ENSP00000258737.7
	RAC1	ENST00000356142.4	TSL:1	c.107+27C>T		intron	N/A	ENSP00000348461.4
	RAC1	ENST00000488373.5	TSL:1	n.338+27C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90919 AN: 151976 Hom.: 29276 Cov.: 33

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.543 AC: 112942 AN: 207992 AF XY: 0.532

Gnomad AFR exome AF: 0.812

Gnomad AMR exome AF: 0.674

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.903

Gnomad FIN exome AF: 0.473

Gnomad NFE exome AF: 0.447

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.503 AC: 649201 AN: 1290776 Hom.: 170650 Cov.: 19 AF XY: 0.503 AC XY: 326689 AN XY: 648906

African (AFR) AF: 0.818 AC: 22186 AN: 27114

American (AMR) AF: 0.669 AC: 21132 AN: 31564

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9162 AN: 24094

East Asian (EAS) AF: 0.904 AC: 32675 AN: 36146

South Asian (SAS) AF: 0.610 AC: 46086 AN: 75546

European-Finnish (FIN) AF: 0.471 AC: 24828 AN: 52740

Middle Eastern (MID) AF: 0.452 AC: 2444 AN: 5412

European-Non Finnish (NFE) AF: 0.469 AC: 461377 AN: 983564

Other (OTH) AF: 0.537 AC: 29311 AN: 54596

GnomAD4 genome AF: 0.599 AC: 91048 AN: 152094 Hom.: 29343 Cov.: 33 AF XY: 0.602 AC XY: 44764 AN XY: 74340

African (AFR) AF: 0.814 AC: 33815 AN: 41518

American (AMR) AF: 0.636 AC: 9701 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4712 AN: 5184

South Asian (SAS) AF: 0.639 AC: 3084 AN: 4826

European-Finnish (FIN) AF: 0.475 AC: 5011 AN: 10554

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31649 AN: 67970

Other (OTH) AF: 0.565 AC: 1192 AN: 2108

Alfa AF: 0.508 Hom.: 3920

Bravo AF: 0.621

Asia WGS AF: 0.816 AC: 2834 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability, autosomal dominant 48 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		0.77
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: rs702483; hg19: chr7-6426941; COSMIC: COSV107421690; COSMIC: COSV107421690;