dbSNP rs1254967: RASGEF1A:c.*1301C>T (chr10-43194943-G-A) – 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.*1301C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,688 control chromosomes in the GnomAD database, including 2,604 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 0.16 ( 2594 hom., cov: 34)

Exomes 𝑓: 0.21 ( 10 hom. )

Consequence

RASGEF1A
NM_145313.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.211

Publications

10 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1A	NM_145313.4 link	c.*1301C>T	3_prime_UTR_variant	Exon 13 of 13	ENST00000395810.6	NP_660356.2	Q8N9B8-1
RASGEF1A	NM_001282862.2 link	c.*1301C>T	3_prime_UTR_variant	Exon 13 of 13		NP_001269791.1	Q8N9B8-2
RASGEF1A	XM_005271809.4 link	c.*1301C>T	3_prime_UTR_variant	Exon 12 of 12		XP_005271866.1
RASGEF1A	XM_011539500.3 link	c.*1301C>T	3_prime_UTR_variant	Exon 12 of 12		XP_011537802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1A	ENST00000395810.6 link	c.*1301C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_145313.4	ENSP00000379155.1		Q8N9B8-1
RASGEF1A	ENST00000374459.5 link	c.*1301C>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000363583.1		Q8N9B8-2

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23637

AN:

152116

Hom.:

2600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0347

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.207

AC:

AN:

454

Hom.:

Cov.:

AF XY:

0.183

AC XY:

AN XY:

290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.224

AC:

AN:

344

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.152

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.155

AC:

23620

AN:

152234

Hom.:

2594

Cov.:

AF XY:

0.159

AC XY:

11824

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0346

AC:

1436

AN:

41562

American (AMR)

AF:

0.191

AC:

2927

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

818

AN:

3468

East Asian (EAS)

AF:

0.499

AC:

2581

AN:

5170

South Asian (SAS)

AF:

0.289

AC:

1394

AN:

4826

European-Finnish (FIN)

AF:

0.179

AC:

1896

AN:

10604

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12067

AN:

67988

Other (OTH)

AF:

0.172

AC:

365

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1005

2009

3014

4018

5023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.166

Hom.:

657

Bravo

AF:

0.148

Asia WGS

AF:

0.372

AC:

1293

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.8

(source)

DANN

Benign

0.66

PhyloP100

0.21

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over