Genetic Variant ENST00000373436.5:c.*462A>G (chr9-127178366-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000373436.5(RALGPS1):c.*462A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 714,826 control chromosomes in the GnomAD database, including 10,710 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 0.14 ( 1898 hom., cov: 33)

Exomes 𝑓: 0.17 ( 8812 hom. )

Consequence

RALGPS1
ENST00000373436.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.434

Publications

8 publications found

Variant links:

Genes affected

RALGPS1 (HGNC:16851): (Ral GEF with PH domain and SH3 binding motif 1) Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Ral protein signal transduction. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RALGPS1 links:

LOC105376278 (HGNC:):

LOC105376278 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=-0.93).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373436.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RALGPS1	NM_014636.3	MANE Select	c.910+3584A>G	intron	N/A	NP_055451.1
RALGPS1	NM_001190730.2		c.*462A>G	3_prime_UTR	Exon 12 of 12	NP_001177659.1
RALGPS1	NM_001322325.2		c.910+3584A>G	intron	N/A	NP_001309254.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RALGPS1	ENST00000373436.5	TSL:1	c.*462A>G	3_prime_UTR	Exon 12 of 12	ENSP00000362535.1
RALGPS1	ENST00000259351.10	TSL:1 MANE Select	c.910+3584A>G	intron	N/A	ENSP00000259351.5
RALGPS1	ENST00000373434.5	TSL:1	c.910+3584A>G	intron	N/A	ENSP00000362533.1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21831

AN:

152192

Hom.:

1901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0731

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.0969

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.173

AC:

97452

AN:

562516

Hom.:

8812

Cov.:

AF XY:

0.174

AC XY:

47203

AN XY:

270534

show subpopulations

African (AFR)

AF:

0.0736

AC:

901

AN:

12238

American (AMR)

AF:

0.277

AC:

1904

AN:

6862

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

1070

AN:

5426

East Asian (EAS)

AF:

0.159

AC:

1314

AN:

8274

South Asian (SAS)

AF:

0.228

AC:

5646

AN:

24758

European-Finnish (FIN)

AF:

0.114

AC:

511

AN:

4492

Middle Eastern (MID)

AF:

0.258

AC:

342

AN:

1324

European-Non Finnish (NFE)

AF:

0.172

AC:

82093

AN:

478490

Other (OTH)

AF:

0.178

AC:

3671

AN:

20652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

3834

7668

11501

15335

19169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3620

7240

10860

14480

18100

<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:

0.143

AC:

21841

AN:

152310

Hom.:

1898

Cov.:

AF XY:

0.143

AC XY:

10685

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0731

AC:

3039

AN:

41572

American (AMR)

AF:

0.237

AC:

3632

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

656

AN:

3470

East Asian (EAS)

AF:

0.170

AC:

881

AN:

5184

South Asian (SAS)

AF:

0.217

AC:

1046

AN:

4826

European-Finnish (FIN)

AF:

0.0969

AC:

1029

AN:

10618

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10924

AN:

68016

Other (OTH)

AF:

0.195

AC:

412

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

998

1996

2994

3992

4990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.163

Hom.:

2371

Bravo

AF:

0.155

Asia WGS

AF:

0.161

AC:

558

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.41

(source)

DANN

Benign

0.41

PhyloP100

-0.43

Mutation Taster

=99/1

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