chr9-126936397-G-A

Variant names:

• chr9-126936397-G-A
• rs488039
• NM_014636.3:c.-66+21422G>A

Variant summary

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

The NM_014636.3(RALGPS1):​c.-66+21422G>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 152,112 control chromosomes in the GnomAD database, including 30,177 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 (30177 hom., cov: 33)
• Consequence: RALGPS1 NM_014636.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014636.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGPS1	NM_014636.3	MANE Select	c.-66+21422G>A		intron	N/A	NP_055451.1
	RALGPS1	NM_001322325.2		c.-66+21385G>A		intron	N/A	NP_001309254.1
	RALGPS1	NM_001322321.2		c.-66+21385G>A		intron	N/A	NP_001309250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGPS1	ENST00000259351.10	TSL:1 MANE Select	c.-66+21422G>A		intron	N/A	ENSP00000259351.5
	RALGPS1	ENST00000373436.5	TSL:1	c.-66+21385G>A		intron	N/A	ENSP00000362535.1
	RALGPS1	ENST00000394011.7	TSL:1	c.-66+21385G>A		intron	N/A	ENSP00000377579.3

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89071 AN: 151994 Hom.: 30176 Cov.: 33

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: 0.768

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: 89079 AN: 152112 Hom.: 30177 Cov.: 33 AF XY: 0.594 AC XY: 44135 AN XY: 74364

African (AFR) AF: 0.230 AC: 9526 AN: 41454

American (AMR) AF: 0.581 AC: 8879 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2334 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4205 AN: 5178

South Asian (SAS) AF: 0.767 AC: 3691 AN: 4814

European-Finnish (FIN) AF: 0.827 AC: 8756 AN: 10590

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49610 AN: 67994

Other (OTH) AF: 0.580 AC: 1226 AN: 2114

Alfa AF: 0.644 Hom.: 4530

Bravo AF: 0.544

Asia WGS AF: 0.760 AC: 2642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.3
DANN	Benign	0.77
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs488039; hg19: chr9-129698676;