Genetic Variant RASGRP3:c.-261+116T>C (chr2-33476823-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_001139488.2(RASGRP3):c.-261+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 145,782 control chromosomes in the GnomAD database, including 382 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 0.064 ( 382 hom., cov: 30)

Exomes 𝑓: 0.014 ( 0 hom. )

Consequence

RASGRP3
NM_001139488.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.700

Publications

63 publications found

Variant links:

Genes affected

RASGRP3 (HGNC:14545): (RAS guanyl releasing protein 3) The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers. [provided by RefSeq, Mar 2017]

RASGRP3 links:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139488.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RASGRP3	NM_001139488.2	MANE Select	c.-261+116T>C	intron	N/A	NP_001132960.1	Q8IV61-1
RASGRP3	NM_001349975.2		c.-382-4360T>C	intron	N/A	NP_001336904.1	Q8IV61-1
RASGRP3	NM_001349976.2		c.-159+116T>C	intron	N/A	NP_001336905.1	Q8IV61-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RASGRP3	ENST00000403687.8	TSL:1 MANE Select	c.-261+116T>C	intron	N/A	ENSP00000384192.3	Q8IV61-1
RASGRP3	ENST00000402538.8	TSL:1	c.-261+28880T>C	intron	N/A	ENSP00000385886.3	Q8IV61-1
RASGRP3	ENST00000850562.1		c.-261+116T>C	intron	N/A	ENSP00000520853.1	A0ABB0MVI6

Frequencies

GnomAD3 genomes

AF:

0.0636

AC:

9245

AN:

145334

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.0586

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0191

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.0535

Gnomad FIN

AF:

0.0408

Gnomad MID

AF:

0.0298

Gnomad NFE

AF:

0.0677

Gnomad OTH

AF:

0.0590

GnomAD4 exome

AF:

0.0138

AC:

AN:

362

Hom.:

AF XY:

0.0112

AC XY:

AN XY:

268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0625

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0131

AC:

AN:

306

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0636

AC:

9252

AN:

145420

Hom.:

382

Cov.:

AF XY:

0.0609

AC XY:

4323

AN XY:

70990

show subpopulations

African (AFR)

AF:

0.0625

AC:

2328

AN:

37232

American (AMR)

AF:

0.0454

AC:

665

AN:

14648

Ashkenazi Jewish (ASJ)

AF:

0.0191

AC:

AN:

3396

East Asian (EAS)

AF:

0.160

AC:

816

AN:

5110

South Asian (SAS)

AF:

0.0534

AC:

240

AN:

4498

European-Finnish (FIN)

AF:

0.0408

AC:

418

AN:

10254

Middle Eastern (MID)

AF:

0.0319

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0677

AC:

4543

AN:

67108

Other (OTH)

AF:

0.0579

AC:

116

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

415

831

1246

1662

2077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0681

Hom.:

1474

Bravo

AF:

0.0616

Asia WGS

AF:

0.0970

AC:

336

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

(source)

DANN

Benign

0.67

PhyloP100

0.70

PromoterAI

0.31

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over