rs10486804

Variant names:

• chr7-39708306-G-A
• rs10486804
• ENST00000791476.1:n.144-7552C>T

Variant summary

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

The ENST00000791476.1(ENSG00000228554):​n.144-7552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 152,254 control chromosomes in the GnomAD database, including 88 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 0.025 (88 hom., cov: 33)
• Consequence: ENSG00000228554 ENST00000791476.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 0 publications found

Genes affected

ENSG00000228554 (HGNC:):

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

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 (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALA	NM_005402.4	c.*2061G>A		downstream_gene_variant		ENST00000005257.7	NP_005393.2
RALA	XM_047420681.1	c.*2061G>A		downstream_gene_variant			XP_047276637.1
RALA	XM_047420682.1	c.*2061G>A		downstream_gene_variant			XP_047276638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228554	ENST00000791476.1	n.144-7552C>T		intron_variant	Intron 1 of 1
ENSG00000228554	ENST00000791477.1	n.253+1868C>T		intron_variant	Intron 2 of 2
RALA	ENST00000005257.7	c.*2061G>A		downstream_gene_variant		1	NM_005402.4	ENSP00000005257.2

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3747 AN: 152136 Hom.: 85 Cov.: 33

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0247 AC: 3758 AN: 152254 Hom.: 88 Cov.: 33 AF XY: 0.0256 AC XY: 1905 AN XY: 74440

African (AFR) AF: 0.0258 AC: 1071 AN: 41544

American (AMR) AF: 0.0376 AC: 576 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3470

East Asian (EAS) AF: 0.144 AC: 745 AN: 5184

South Asian (SAS) AF: 0.0543 AC: 262 AN: 4822

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 857 AN: 68010

Other (OTH) AF: 0.0232 AC: 49 AN: 2112

Alfa AF: 0.0171 Hom.: 79

Bravo AF: 0.0271

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.75
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10486804; hg19: chr7-39747905;