chr9-133098713-G-A

Position:

• chr9-133098713-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_006266.4(RALGDS):​c.2619C>T​(p.Thr873Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,613,596 control chromosomes in the GnomAD database, including 228,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.47 (17998 hom., cov: 32)
  • Exomes 𝑓: 0.53 (210535 hom.)
• Consequence: RALGDS NM_006266.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

Genes affected

RALGDS (HGNC:9842): (ral guanine nucleotide dissociation stimulator) Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes.[supplied by OMIM, Nov 2010]

ENSG00000285245 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-133098713-G-A is Benign according to our data. Variant chr9-133098713-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGDS	NM_006266.4	c.2619C>T	p.Thr873Thr	synonymous_variant	18/18	ENST00000372050.8	NP_006257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGDS	ENST00000372050.8	c.2619C>T	p.Thr873Thr	synonymous_variant	18/18	1	NM_006266.4	ENSP00000361120.3
ENSG00000285245	ENST00000647146.1	c.2832C>T	p.Thr944Thr	synonymous_variant	23/23			ENSP00000493691.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71858 AN: 151982 Hom.: 17990 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.467

GnomAD3 exomes AF: 0.545 AC: 136598 AN: 250712 Hom.: 38249 AF XY: 0.553 AC XY: 74908 AN XY: 135578

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.575

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.626

Gnomad SAS exome AF: 0.660

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.534

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.534 AC: 779784 AN: 1461496 Hom.: 210535 Cov.: 53 AF XY: 0.539 AC XY: 391577 AN XY: 727076

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.589

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.524

GnomAD4 genome AF: 0.473 AC: 71893 AN: 152100 Hom.: 17998 Cov.: 32 AF XY: 0.478 AC XY: 35513 AN XY: 74360

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.470

Alfa AF: 0.491 Hom.: 10662

Bravo AF: 0.460

Asia WGS AF: 0.602 AC: 2092 AN: 3478

EpiCase AF: 0.522

EpiControl AF: 0.526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.15
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs886017; hg19: chr9-135974100; COSMIC: COSV64426175; COSMIC: COSV64426175;