Genetic Variant RALBP1:c.1053+99G>A (chr18-9522608-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_006788.4(RALBP1):c.1053+99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 966,870 control chromosomes in the GnomAD database, including 280,615 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 0.78 ( 47211 hom., cov: 33)

Exomes 𝑓: 0.75 ( 233404 hom. )

Consequence

RALBP1
NM_006788.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.175

Publications

15 publications found

Variant links:

Genes affected

RALBP1 (HGNC:9841): (ralA binding protein 1) RALBP1 plays a role in receptor-mediated endocytosis and is a downstream effector of the small GTP-binding protein RAL (see RALA; MIM 179550). Small G proteins, such as RAL, have GDP-bound inactive and GTP-bound active forms, which shift from the inactive to the active state through the action of RALGDS (MIM 601619), which in turn is activated by RAS (see HRAS; MIM 190020) (summary by Feig, 2003 [PubMed 12888294]).[supplied by OMIM, Nov 2010]

RALBP1 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006788.4. 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
	RALBP1	NM_006788.4	MANE Select	c.1053+99G>A		intron	N/A	NP_006779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALBP1	ENST00000383432.8	TSL:1 MANE Select	c.1053+99G>A		intron	N/A	ENSP00000372924.3
	RALBP1	ENST00000019317.8	TSL:1	c.1053+99G>A		intron	N/A	ENSP00000019317.4

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119331

AN:

152132

Hom.:

47168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.841

Gnomad AMI

AF:

0.816

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.584

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.781

GnomAD4 exome

AF:

0.754

AC:

613927

AN:

814618

Hom.:

233404

AF XY:

0.748

AC XY:

310059

AN XY:

414336

show subpopulations

African (AFR)

AF:

0.848

AC:

16311

AN:

19242

American (AMR)

AF:

0.721

AC:

17412

AN:

24134

Ashkenazi Jewish (ASJ)

AF:

0.791

AC:

13116

AN:

16580

East Asian (EAS)

AF:

0.578

AC:

19695

AN:

34050

South Asian (SAS)

AF:

0.612

AC:

33871

AN:

55358

European-Finnish (FIN)

AF:

0.857

AC:

31351

AN:

36598

Middle Eastern (MID)

AF:

0.817

AC:

3542

AN:

4336

European-Non Finnish (NFE)

AF:

0.767

AC:

449432

AN:

585970

Other (OTH)

AF:

0.761

AC:

29197

AN:

38350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

7484

14969

22453

29938

37422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8360

16720

25080

33440

41800

<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:

0.784

AC:

119434

AN:

152252

Hom.:

47211

Cov.:

AF XY:

0.782

AC XY:

58226

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.841

AC:

34954

AN:

41554

American (AMR)

AF:

0.744

AC:

11380

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.796

AC:

2764

AN:

3472

East Asian (EAS)

AF:

0.584

AC:

3022

AN:

5176

South Asian (SAS)

AF:

0.606

AC:

2928

AN:

4828

European-Finnish (FIN)

AF:

0.866

AC:

9185

AN:

10608

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.773

AC:

52572

AN:

67996

Other (OTH)

AF:

0.776

AC:

1641

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1306

2612

3918

5224

6530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.769

Hom.:

142422

Bravo

AF:

0.780

Asia WGS

AF:

0.566

AC:

1970

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.75

(source)

DANN

Benign

0.62

PhyloP100

-0.17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over