9-127009592-T-C

Position:

• chr9-127009592-T-C

Variant summary

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

The NM_014636.3(RALGPS1):​c.217-24839T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,082 control chromosomes in the GnomAD database, including 12,645 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 0.38 (12645 hom., cov: 32)
• Consequence: RALGPS1 NM_014636.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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
RALGPS1	NM_014636.3	c.217-24839T>C		intron_variant		ENST00000259351.10	NP_055451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGPS1	ENST00000259351.10	c.217-24839T>C		intron_variant		1	NM_014636.3	ENSP00000259351.5

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57379 AN: 151964 Hom.: 12651 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.377 AC: 57377 AN: 152082 Hom.: 12645 Cov.: 32 AF XY: 0.380 AC XY: 28283 AN XY: 74332

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.358

Alfa AF: 0.447 Hom.: 7552

Bravo AF: 0.350

Asia WGS AF: 0.301 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1536705; hg19: chr9-129771871;