rs2454217

Positions:

• chr9-126917654-G-A
• chr9-126917654-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014636.3(RALGPS1):​c.-66+2679G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,136 control chromosomes in the GnomAD database, including 30,181 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 0.59 (30181 hom., cov: 32)
• Consequence: RALGPS1 NM_014636.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

RALGPS1 (HGNC:16851): (Ral GEF with PH domain and SH3 binding motif 1) Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Ral protein signal transduction. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RALGPS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGPS1	NM_014636.3	c.-66+2679G>A		intron_variant		ENST00000259351.10	NP_055451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGPS1	ENST00000259351.10	c.-66+2679G>A		intron_variant		1	NM_014636.3	ENSP00000259351.5

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89095 AN: 152018 Hom.: 30180 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.586 AC: 89104 AN: 152136 Hom.: 30181 Cov.: 32 AF XY: 0.593 AC XY: 44149 AN XY: 74390

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.580

Alfa AF: 0.659 Hom.: 4490

Bravo AF: 0.545

Asia WGS AF: 0.760 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.6
DANN	Benign	0.58

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: rs2454217; hg19: chr9-129679933;