Genetic Variant NM_145313.4: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:

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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 (EAS) allele frequency at 95% confidence interval = 0.481 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	NM_145313.4	MANE Select	c.-6-573G>A		intron	N/A	NP_660356.2
	RASGEF1A	NM_001282862.2		c.19-573G>A		intron	N/A	NP_001269791.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.-6-573G>A	intron	N/A	ENSP00000379155.1
RASGEF1A	ENST00000395809.5	TSL:2	c.-18G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000379154.1
RASGEF1A	ENST00000395809.5	TSL:2	c.-18G>A	5_prime_UTR	Exon 1 of 13	ENSP00000379154.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over