17-17494964-G-A

Position:

• chr17-17494964-G-A

Variant summary

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

The NM_016084.5(RASD1):​c.*161C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 872,972 control chromosomes in the GnomAD database, including 23,333 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 0.20 (3260 hom., cov: 33)
  • Exomes 𝑓: 0.23 (20073 hom.)
• Consequence: RASD1 NM_016084.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASD1	NM_016084.5	c.*161C>T		3_prime_UTR_variant	2/2	ENST00000225688.4	NP_057168.1
RASD1	NM_001199989.2	c.*564C>T		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.*161C>T		3_prime_UTR_variant	2/2	1	NM_016084.5	ENSP00000225688.3
RASD1	ENST00000579152.1	c.*564C>T		3_prime_UTR_variant	2/2	2		ENSP00000463388.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30226 AN: 152044 Hom.: 3260 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.231 AC: 166735 AN: 720810 Hom.: 20073 Cov.: 10 AF XY: 0.233 AC XY: 85332 AN XY: 366586

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.0802

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.199 AC: 30236 AN: 152162 Hom.: 3260 Cov.: 33 AF XY: 0.195 AC XY: 14499 AN XY: 74402

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0736

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.205

Alfa AF: 0.228 Hom.: 873

Bravo AF: 0.193

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.93

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: rs11545787; hg19: chr17-17398278;