rs10486802

Positions:

• chr7-39684169-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALA	NM_005402.4	c.-37-2462G>A		intron_variant		ENST00000005257.7	NP_005393.2
RALA	XM_047420681.1	c.-37-2462G>A		intron_variant			XP_047276637.1
RALA	XM_047420682.1	c.-37-2462G>A		intron_variant			XP_047276638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALA	ENST00000005257.7	c.-37-2462G>A		intron_variant		1	NM_005402.4	ENSP00000005257	P1
RALA	ENST00000436179.1	c.-37-2462G>A		intron_variant		2		ENSP00000388975
RALA	ENST00000468201.1	n.262-12516G>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.390

Alfa AF: 0.459 Hom.: 22297

Bravo AF: 0.410

Asia WGS AF: 0.270 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.28

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

LitVar

Other links and lift over

dbSNP: rs10486802; hg19: chr7-39723768;