Genetic Variant RASGRP3:c.-261+16481T>C (chr2-33493188-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+16481T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,076 control chromosomes in the GnomAD database, including 8,756 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 0.33 ( 8755 hom., cov: 32)

Exomes 𝑓: 0.24 ( 1 hom. )

Consequence

RASGRP3
NM_001139488.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.717

Publications

2 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 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+16481T>C	intron	N/A	NP_001132960.1	Q8IV61-1
RASGRP3	NM_001349975.2		c.-261+11884T>C	intron	N/A	NP_001336904.1	Q8IV61-1
RASGRP3	NM_001349976.2		c.-159+16481T>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+16481T>C	intron	N/A	ENSP00000384192.3	Q8IV61-1
RASGRP3	ENST00000402538.8	TSL:1	c.-260-18522T>C	intron	N/A	ENSP00000385886.3	Q8IV61-1
RASGRP3	ENST00000850562.1		c.-261+16481T>C	intron	N/A	ENSP00000520853.1	A0ABB0MVI6

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49706

AN:

151924

Hom.:

8727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.277

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.294

GnomAD4 exome

AF:

0.235

AC:

AN:

Hom.:

Cov.:

AF XY:

0.233

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.328

AC:

49796

AN:

152042

Hom.:

8755

Cov.:

AF XY:

0.331

AC XY:

24634

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.419

AC:

17376

AN:

41464

American (AMR)

AF:

0.376

AC:

5748

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

776

AN:

3470

East Asian (EAS)

AF:

0.378

AC:

1950

AN:

5160

South Asian (SAS)

AF:

0.312

AC:

1500

AN:

4812

European-Finnish (FIN)

AF:

0.317

AC:

3355

AN:

10574

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18065

AN:

67960

Other (OTH)

AF:

0.300

AC:

633

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1661

3321

4982

6642

8303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.286

Hom.:

10921

Bravo

AF:

0.335

Asia WGS

AF:

0.377

AC:

1309

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.49

(source)

DANN

Benign

0.44

PhyloP100

-0.72

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over