Genetic Variant RASGEF1A:c.849+75A>T (chr10-43199601-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145313.4(RASGEF1A):c.849+75A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,224,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 9.3e-7 ( 0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RASGEF1A	NM_145313.4 link	c.849+75A>T	intron_variant	Intron 7 of 12	ENST00000395810.6	NP_660356.2
RASGEF1A	NM_001282862.2 link	c.873+75A>T	intron_variant	Intron 7 of 12		NP_001269791.1
RASGEF1A	XM_005271809.4 link	c.609+75A>T	intron_variant	Intron 6 of 11		XP_005271866.1
RASGEF1A	XM_011539500.3 link	c.609+75A>T	intron_variant	Intron 6 of 11		XP_011537802.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
RASGEF1A	ENST00000395810.6 link	c.849+75A>T	intron_variant	Intron 7 of 12	1	NM_145313.4	ENSP00000379155.1
RASGEF1A	ENST00000374459.5 link	c.873+75A>T	intron_variant	Intron 7 of 12	2		ENSP00000363583.1
RASGEF1A	ENST00000395809.5 link	c.849+75A>T	intron_variant	Intron 7 of 12	2		ENSP00000379154.1
RASGEF1A	ENST00000374455.2 link	c.552+75A>T	intron_variant	Intron 5 of 5	5		ENSP00000363579.2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.32e-7

AC:

AN:

1072846

Hom.:

AF XY:

0.00000182

AC XY:

AN XY:

548778

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26132

American (AMR)

AF:

0.0000243

AC:

AN:

41072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23426

East Asian (EAS)

AF:

0.00

AC:

AN:

37332

South Asian (SAS)

AF:

0.00

AC:

AN:

76822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

770598

Other (OTH)

AF:

0.00

AC:

AN:

47872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

34672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

(source)

DANN

Benign

0.75

PhyloP100

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over