4-9783641-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000798.5(DRD5):c.*178G>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 0.568 in 645,872 control chromosomes in the GnomAD database, including 109,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22412 hom., cov: 31)
  • Exomes 𝑓: 0.58 (87296 hom.)
• Consequence: DRD5 NM_000798.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.654

Genes affected

DRD5 (HGNC:3026): (dopamine receptor D5) This gene encodes the D5 subtype of the dopamine receptor. The D5 subtype is a G-protein coupled receptor which stimulates adenylyl cyclase. This receptor is expressed in neurons in the limbic regions of the brain. It has a 10-fold higher affinity for dopamine than the D1 subtype. Pseudogenes related to this gene reside on chromosomes 1 and 2. [provided by RefSeq, Jul 2008]

SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-9783641-G-T is Benign according to our data. Variant chr4-9783641-G-T is described in ClinVar as [Benign]. Clinvar id is 1270964.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD5	NM_000798.5	c.*178G>T		3_prime_UTR_variant	1/1	ENST00000304374.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD5	ENST00000304374.4	c.*178G>T		3_prime_UTR_variant	1/1		NM_000798.5	P1
SLC2A9	ENST00000503803.5	n.386-3576C>A		intron_variant, non_coding_transcript_variant		3
SLC2A9	ENST00000508585.5	n.182-12272C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79716 AN: 151644 Hom.: 22401 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.581 AC: 287224 AN: 494110 Hom.: 87296 Cov.: 6 AF XY: 0.577 AC XY: 147807 AN XY: 256372

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.525 AC: 79743 AN: 151762 Hom.: 22412 Cov.: 31 AF XY: 0.521 AC XY: 38605 AN XY: 74132

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.527

Alfa AF: 0.522 Hom.: 4061

Bravo AF: 0.508

Asia WGS AF: 0.321 AC: 1114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.4
Dann	Benign	0.77

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: rs1967550; hg19: chr4-9785265; COSMIC: COSV58577677;