rs1890546

Positions:

• chr9-127189862-G-A
• chr9-127189862-G-C

Variant summary

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

The NM_014636.3(RALGPS1):​c.911-5229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,154 control chromosomes in the GnomAD database, including 21,639 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 0.53 (21639 hom., cov: 33)
• Consequence: RALGPS1 NM_014636.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGPS1	NM_014636.3	c.911-5229G>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.911-5229G>A		intron_variant		1	NM_014636.3	ENSP00000259351.5
RALGPS1	ENST00000373434.5	c.911-5229G>A		intron_variant		1		ENSP00000362533.1
RALGPS1	ENST00000424082.6	c.911-5229G>A		intron_variant		2		ENSP00000415630.2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80213 AN: 152036 Hom.: 21618 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.528 AC: 80292 AN: 152154 Hom.: 21639 Cov.: 33 AF XY: 0.527 AC XY: 39242 AN XY: 74398

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.581

Alfa AF: 0.531 Hom.: 9988

Bravo AF: 0.541

Asia WGS AF: 0.688 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.32

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: rs1890546; hg19: chr9-129952141;