dbSNP rs1254958: RASGEF1A:c.-6-573G>A (chr10-43206695-C-T) – 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.-6-573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 986,606 control chromosomes in the GnomAD database, including 15,455 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 ( 2616 hom., cov: 33)

Exomes 𝑓: 0.17 ( 12839 hom. )

Consequence

RASGEF1A
NM_145313.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

7 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1A	NM_145313.4 link	c.-6-573G>A		intron_variant	Intron 1 of 12	ENST00000395810.6	NP_660356.2	Q8N9B8-1
RASGEF1A	NM_001282862.2 link	c.19-573G>A		intron_variant	Intron 1 of 12		NP_001269791.1	Q8N9B8-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RASGEF1A	ENST00000395810.6 link	c.-6-573G>A	intron_variant	Intron 1 of 12	1	NM_145313.4	ENSP00000379155.1	Q8N9B8-1
RASGEF1A	ENST00000395809.5 link	c.-18G>A	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	2		ENSP00000379154.1	Q8N9B8-1
RASGEF1A	ENST00000395809.5 link	c.-18G>A	5_prime_UTR_variant	Exon 1 of 13	2		ENSP00000379154.1	Q8N9B8-1
RASGEF1A	ENST00000374459.5 link	c.19-573G>A	intron_variant	Intron 1 of 12	2		ENSP00000363583.1	Q8N9B8-2

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24460

AN:

152004

Hom.:

2622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.172

AC:

143360

AN:

834484

Hom.:

12839

Cov.:

AF XY:

0.172

AC XY:

66381

AN XY:

385478

show subpopulations

African (AFR)

AF:

0.0436

AC:

688

AN:

15794

American (AMR)

AF:

0.224

AC:

266

AN:

1190

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

1207

AN:

5164

East Asian (EAS)

AF:

0.479

AC:

1741

AN:

3636

South Asian (SAS)

AF:

0.253

AC:

4183

AN:

16504

European-Finnish (FIN)

AF:

0.162

AC:

AN:

296

Middle Eastern (MID)

AF:

0.212

AC:

345

AN:

1624

European-Non Finnish (NFE)

AF:

0.170

AC:

129331

AN:

762914

Other (OTH)

AF:

0.203

AC:

5551

AN:

27362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

7344

14687

22031

29374

36718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6340

12680

19020

25360

31700

<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:

0.161

AC:

24443

AN:

152122

Hom.:

2616

Cov.:

AF XY:

0.164

AC XY:

12192

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0545

AC:

2265

AN:

41528

American (AMR)

AF:

0.193

AC:

2951

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

817

AN:

3470

East Asian (EAS)

AF:

0.497

AC:

2553

AN:

5134

South Asian (SAS)

AF:

0.289

AC:

1390

AN:

4818

European-Finnish (FIN)

AF:

0.179

AC:

1896

AN:

10594

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12061

AN:

67972

Other (OTH)

AF:

0.177

AC:

375

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1018

2037

3055

4074

5092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.171

Hom.:

555

Bravo

AF:

0.154

Asia WGS

AF:

0.370

AC:

1287

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.053

(source)

DANN

Benign

0.58

PhyloP100

-1.2

Mutation Taster

=300/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over