Genetic Variant RASGRF2:c.544-510T>C (chr5-81069982-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006909.3(RASGRF2):c.544-510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 154,980 control chromosomes in the GnomAD database, including 6,121 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 0.27 ( 5988 hom., cov: 33)

Exomes 𝑓: 0.29 ( 133 hom. )

Consequence

RASGRF2
NM_006909.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

1 publications found

Variant links:

Genes affected

RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

RASGRF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3 link	c.544-510T>C		intron_variant	Intron 3 of 26	ENST00000265080.9	NP_008840.1	O14827Q68DX5A0A2X0SFL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9 link	c.544-510T>C		intron_variant	Intron 3 of 26	1	NM_006909.3	ENSP00000265080.4		O14827

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41211

AN:

152086

Hom.:

5991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.289

AC:

802

AN:

2776

Hom.:

133

Cov.:

AF XY:

0.287

AC XY:

422

AN XY:

1470

show subpopulations

African (AFR)

AF:

0.107

AC:

AN:

American (AMR)

AF:

0.363

AC:

196

AN:

540

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

AN:

East Asian (EAS)

AF:

0.115

AC:

AN:

148

South Asian (SAS)

AF:

0.252

AC:

AN:

202

European-Finnish (FIN)

AF:

0.222

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.291

AC:

497

AN:

1708

Other (OTH)

AF:

0.232

AC:

AN:

112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.271

AC:

41213

AN:

152204

Hom.:

5988

Cov.:

AF XY:

0.271

AC XY:

20185

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.171

AC:

7087

AN:

41542

American (AMR)

AF:

0.358

AC:

5464

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

935

AN:

3468

East Asian (EAS)

AF:

0.130

AC:

673

AN:

5186

South Asian (SAS)

AF:

0.278

AC:

1339

AN:

4824

European-Finnish (FIN)

AF:

0.319

AC:

3372

AN:

10582

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21448

AN:

68004

Other (OTH)

AF:

0.264

AC:

556

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1534

3068

4601

6135

7669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.306

Hom.:

4779

Bravo

AF:

0.271

Asia WGS

AF:

0.200

AC:

698

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.6

(source)

DANN

Benign

0.70

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over