17-17494504-G-C

Position:

• chr17-17494504-G-C

Variant summary

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

The NM_016084.5(RASD1):​c.*621C>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 0.683 in 151,206 control chromosomes in the GnomAD database, including 35,894 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 0.68 (35773 hom., cov: 28)
  • Exomes 𝑓: 0.73 (121 hom.)
• Consequence: RASD1 NM_016084.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

Genes affected

RASD1 (HGNC:15828): (ras related dexamethasone induced 1) This gene encodes a member of the Ras superfamily of small GTPases and is induced by dexamethasone. The encoded protein is an activator of G-protein signaling and acts as a direct nucleotide exchange factor for Gi-Go proteins. This protein interacts with the neuronal nitric oxide adaptor protein CAPON, and a nuclear adaptor protein FE65, which interacts with the Alzheimer's disease amyloid precursor protein. This gene may play a role in dexamethasone-induced alterations in cell morphology, growth and cell-extracellular matrix interactions. Epigenetic inactivation of this gene is closely correlated with resistance to dexamethasone in multiple myeloma cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASD1	NM_016084.5	c.*621C>G		3_prime_UTR_variant	2/2	ENST00000225688.4	NP_057168.1
RASD1	NM_001199989.2	c.*1024C>G		3_prime_UTR_variant	2/2		NP_001186918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASD1	ENST00000225688.4	c.*621C>G		3_prime_UTR_variant	2/2	1	NM_016084.5	ENSP00000225688.3

Frequencies

GnomAD3 genomes AF: 0.683 AC: 102925 AN: 150650 Hom.: 35755 Cov.: 28

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.681

GnomAD4 exome AF: 0.725 AC: 322 AN: 444 Hom.: 121 Cov.: 0 AF XY: 0.743 AC XY: 199 AN XY: 268

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.721

Gnomad4 NFE exome AF: 0.813

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.683 AC: 102999 AN: 150762 Hom.: 35773 Cov.: 28 AF XY: 0.677 AC XY: 49768 AN XY: 73566

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.678

Alfa AF: 0.655 Hom.: 1997

Bravo AF: 0.673

Asia WGS AF: 0.448 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.71

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: rs711352; hg19: chr17-17397818; COSMIC: COSV51957552; COSMIC: COSV51957552;