Genetic Variant RASGEF1A:c.849+75A>G (chr10-43199601-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_145313.4(RASGEF1A):c.849+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,223,124 control chromosomes in the GnomAD database, including 334,250 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 0.76 ( 44577 hom., cov: 33)

Exomes 𝑓: 0.73 ( 289673 hom. )

Consequence

RASGEF1A
NM_145313.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106

Publications

12 publications found

Variant links:

Genes affected

RASGEF1A (HGNC:24246): (RasGEF domain family member 1A) Enables guanyl-nucleotide exchange factor activity. Involved in cell migration and positive regulation of Ras protein signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RASGEF1A 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145313.4. 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
	RASGEF1A	NM_145313.4	MANE Select	c.849+75A>G		intron	N/A	NP_660356.2	Q8N9B8-1
	RASGEF1A	NM_001282862.2		c.873+75A>G		intron	N/A	NP_001269791.1	Q8N9B8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.849+75A>G	intron	N/A	ENSP00000379155.1	Q8N9B8-1
RASGEF1A	ENST00000954344.1		c.885+75A>G	intron	N/A	ENSP00000624403.1
RASGEF1A	ENST00000374459.5	TSL:2	c.873+75A>G	intron	N/A	ENSP00000363583.1	Q8N9B8-2

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

116032

AN:

152080

Hom.:

44522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.808

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.776

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.804

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.762

GnomAD4 exome

AF:

0.733

AC:

784991

AN:

1070926

Hom.:

289673

AF XY:

0.736

AC XY:

403392

AN XY:

547806

show subpopulations

African (AFR)

AF:

0.812

AC:

21196

AN:

26110

American (AMR)

AF:

0.786

AC:

32291

AN:

41062

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

17023

AN:

23410

East Asian (EAS)

AF:

0.932

AC:

34810

AN:

37332

South Asian (SAS)

AF:

0.839

AC:

64425

AN:

76778

European-Finnish (FIN)

AF:

0.788

AC:

34996

AN:

44432

Middle Eastern (MID)

AF:

0.820

AC:

4189

AN:

5110

European-Non Finnish (NFE)

AF:

0.703

AC:

540611

AN:

768880

Other (OTH)

AF:

0.741

AC:

35450

AN:

47812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

10996

21992

32988

43984

54980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11596

23192

34788

46384

57980

<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:

0.763

AC:

116148

AN:

152198

Hom.:

44577

Cov.:

AF XY:

0.769

AC XY:

57245

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.808

AC:

33573

AN:

41536

American (AMR)

AF:

0.777

AC:

11882

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

2559

AN:

3470

East Asian (EAS)

AF:

0.939

AC:

4842

AN:

5158

South Asian (SAS)

AF:

0.850

AC:

4099

AN:

4822

European-Finnish (FIN)

AF:

0.804

AC:

8517

AN:

10592

Middle Eastern (MID)

AF:

0.806

AC:

237

AN:

294

European-Non Finnish (NFE)

AF:

0.709

AC:

48195

AN:

68002

Other (OTH)

AF:

0.764

AC:

1617

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1424

2848

4273

5697

7121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.722

Hom.:

34672

Bravo

AF:

0.761

Asia WGS

AF:

0.879

AC:

3055

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.3

(source)

DANN

Benign

0.80

PhyloP100

0.11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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