dbSNP rs7778955: RALA:c.498+4029A>G (chr7-39700888-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 NM_005402.4(RALA):c.498+4029A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,134 control chromosomes in the GnomAD database, including 8,232 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 0.31 ( 8232 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

RALA
NM_005402.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.180

Publications

5 publications found

Variant links:

Genes affected

RALA (HGNC:9839): (RAS like proto-oncogene A) The product of this gene belongs to the small GTPase superfamily, Ras family of proteins. GTP-binding proteins mediate the transmembrane signaling initiated by the occupancy of certain cell surface receptors. This gene encodes a low molecular mass ras-like GTP-binding protein that shares about 50% similarity with other ras proteins. [provided by RefSeq, Jul 2008]

RALA Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
Hiatt-Neu-Cooper neurodevelopmental syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

RALA links:

ENSG00000228554 (HGNC:):

ENSG00000228554 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005402.4. 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
	RALA	NM_005402.4	MANE Select	c.498+4029A>G		intron	N/A	NP_005393.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RALA	ENST00000005257.7	TSL:1 MANE Select	c.498+4029A>G	intron	N/A	ENSP00000005257.2
RALA	ENST00000466491.1	TSL:3	n.9A>G	non_coding_transcript_exon	Exon 1 of 2
RALA	ENST00000434466.1	TSL:3	n.*88+3378A>G	intron	N/A	ENSP00000413227.1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47625

AN:

152014

Hom.:

8235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.280

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.313

AC:

47634

AN:

152132

Hom.:

8232

Cov.:

AF XY:

0.309

AC XY:

22975

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.231

AC:

9595

AN:

41508

American (AMR)

AF:

0.219

AC:

3357

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

943

AN:

3468

East Asian (EAS)

AF:

0.0338

AC:

175

AN:

5172

South Asian (SAS)

AF:

0.346

AC:

1668

AN:

4814

European-Finnish (FIN)

AF:

0.357

AC:

3771

AN:

10572

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.396

AC:

26922

AN:

67982

Other (OTH)

AF:

0.277

AC:

586

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1636

3272

4909

6545

8181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.361

Hom.:

44661

Bravo

AF:

0.298

Asia WGS

AF:

0.206

AC:

720

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.9

(source)

DANN

Benign

0.58

PhyloP100

0.18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over