rs10486802

Variant names:

• chr7-39684169-G-A
• rs10486802
• NM_005402.4:c.-37-2462G>A

Variant summary

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

The NM_005402.4(RALA):​c.-37-2462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,914 control chromosomes in the GnomAD database, including 14,159 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 0.42 (14159 hom., cov: 31)
• Consequence: RALA NM_005402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 8 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 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.-37-2462G>A		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.-37-2462G>A		intron	N/A	ENSP00000005257.2	P11233
	RALA	ENST00000860175.1		c.-37-2462G>A		intron	N/A	ENSP00000530234.1
	RALA	ENST00000860176.1		c.-37-2462G>A		intron	N/A	ENSP00000530235.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63966 AN: 151796 Hom.: 14154 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.421 AC: 63996 AN: 151914 Hom.: 14159 Cov.: 31 AF XY: 0.414 AC XY: 30731 AN XY: 74226

African (AFR) AF: 0.404 AC: 16743 AN: 41392

American (AMR) AF: 0.295 AC: 4506 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.102 AC: 526 AN: 5166

South Asian (SAS) AF: 0.429 AC: 2070 AN: 4820

European-Finnish (FIN) AF: 0.422 AC: 4448 AN: 10532

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32843 AN: 67950

Other (OTH) AF: 0.390 AC: 825 AN: 2116

Alfa AF: 0.454 Hom.: 27682

Bravo AF: 0.410

Asia WGS AF: 0.270 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.28
PhyloP100		-0.34
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: rs10486802; hg19: chr7-39723768;