NM_005402.4:c.498+4029A>G

Variant names:

• chr7-39700888-A-G
• rs7778955
• NM_005402.4:c.498+4029A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 5 publications found

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: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics
• Hiatt-Neu-Cooper neurodevelopmental syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000228554 (HGNC:):

ACMG classification

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

Sel.	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALA	ENST00000005257.7	TSL:1 MANE Select	c.498+4029A>G		intron	N/A	ENSP00000005257.2	P11233
	RALA	ENST00000860175.1		c.498+4029A>G		intron	N/A	ENSP00000530234.1
	RALA	ENST00000860176.1		c.498+4029A>G		intron	N/A	ENSP00000530235.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47625 AN: 152014 Hom.: 8235 Cov.: 32

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: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.313 AC: 47634 AN: 152132 Hom.: 8232 Cov.: 32 AF XY: 0.309 AC XY: 22975 AN XY: 74376

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: 94 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26922 AN: 67982

Other (OTH) AF: 0.277 AC: 586 AN: 2114

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
DANN	Benign	0.58
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7778955; hg19: chr7-39740487;