rs3739554

Positions:

• chr9-127178366-A-G

Variant summary

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

The ENST00000373436.5(RALGPS1):​c.*462A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 714,826 control chromosomes in the GnomAD database, including 10,710 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 0.14 (1898 hom., cov: 33)
  • Exomes 𝑓: 0.17 (8812 hom.)
• Consequence: RALGPS1 ENST00000373436.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

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]

LOC105376278 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGPS1	NM_014636.3	c.910+3584A>G		intron_variant		ENST00000259351.10	NP_055451.1
LOC105376278	XR_007061789.1	n.1577T>C		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGPS1	ENST00000259351.10	c.910+3584A>G		intron_variant		1	NM_014636.3	ENSP00000259351	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21831 AN: 152192 Hom.: 1901 Cov.: 33

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.173 AC: 97452 AN: 562516 Hom.: 8812 Cov.: 8 AF XY: 0.174 AC XY: 47203 AN XY: 270534

Gnomad4 AFR exome AF: 0.0736

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.143 AC: 21841 AN: 152310 Hom.: 1898 Cov.: 33 AF XY: 0.143 AC XY: 10685 AN XY: 74480

Gnomad4 AFR AF: 0.0731

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.195

Alfa AF: 0.165 Hom.: 1205

Bravo AF: 0.155

Asia WGS AF: 0.161 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.41

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: rs3739554; hg19: chr9-129940645;