9-126953457-A-G

Position:

• chr9-126953457-A-G

Variant summary

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

The NM_014636.3(RALGPS1):​c.-65-8768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,862 control chromosomes in the GnomAD database, including 30,114 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 (30114 hom., cov: 30)
• Consequence: RALGPS1 NM_014636.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGPS1	NM_014636.3	c.-65-8768A>G		intron_variant		ENST00000259351.10	NP_055451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGPS1	ENST00000259351.10	c.-65-8768A>G		intron_variant		1	NM_014636.3	ENSP00000259351	P1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88901 AN: 151744 Hom.: 30113 Cov.: 30

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.812

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: 0.585 AC: 88910 AN: 151862 Hom.: 30114 Cov.: 30 AF XY: 0.593 AC XY: 44024 AN XY: 74226

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.581

Alfa AF: 0.702 Hom.: 79239

Bravo AF: 0.544

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	-0.95
CADD	Benign	0.77
DANN	Benign	0.31

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: rs518116; hg19: chr9-129715736;