rs3739554

Variant names:

• chr9-127178366-A-G
• rs3739554
• ENST00000373436.5:c.*462A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

LOC105376278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RALGPS1	NM_014636.3	c.910+3584A>G		intron_variant	Intron 11 of 18	ENST00000259351.10	NP_055451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALGPS1	ENST00000259351.10	c.910+3584A>G		intron_variant	Intron 11 of 18	1	NM_014636.3	ENSP00000259351.5

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

African (AFR) AF: 0.0736 AC: 901 AN: 12238

American (AMR) AF: 0.277 AC: 1904 AN: 6862

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 1070 AN: 5426

East Asian (EAS) AF: 0.159 AC: 1314 AN: 8274

South Asian (SAS) AF: 0.228 AC: 5646 AN: 24758

European-Finnish (FIN) AF: 0.114 AC: 511 AN: 4492

Middle Eastern (MID) AF: 0.258 AC: 342 AN: 1324

European-Non Finnish (NFE) AF: 0.172 AC: 82093 AN: 478490

Other (OTH) AF: 0.178 AC: 3671 AN: 20652

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

African (AFR) AF: 0.0731 AC: 3039 AN: 41572

American (AMR) AF: 0.237 AC: 3632 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3470

East Asian (EAS) AF: 0.170 AC: 881 AN: 5184

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4826

European-Finnish (FIN) AF: 0.0969 AC: 1029 AN: 10618

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10924 AN: 68016

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.163 Hom.: 2371

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
PhyloP100		-0.43
Mutation Taster		=99/1	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: rs3739554; hg19: chr9-129940645;