rs6281

Positions:

• chr4-9783265-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000798.5(DRD5):​c.1236C>T​(p.His412His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,614,214 control chromosomes in the GnomAD database, including 251 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 0.0055 (30 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (221 hom.)
• Consequence: DRD5 NM_000798.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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]

SLC2A9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.082 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD5	NM_000798.5	c.1236C>T	p.His412His	synonymous_variant	1/1	ENST00000304374.4	NP_000789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD5	ENST00000304374.4	c.1236C>T	p.His412His	synonymous_variant	1/1	6	NM_000798.5	ENSP00000306129.2
SLC2A9	ENST00000503803.5	n.386-3200G>A		intron_variant		3
SLC2A9	ENST00000508585.5	n.182-11896G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 842 AN: 152204 Hom.: 30 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0796

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.0125 AC: 3136 AN: 251462 Hom.: 110 AF XY: 0.0140 AC XY: 1906 AN XY: 135918

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0836

Gnomad SAS exome AF: 0.0450

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000994

Gnomad OTH exome AF: 0.00896

GnomAD4 exome AF: 0.00536 AC: 7829 AN: 1461894 Hom.: 221 Cov.: 36 AF XY: 0.00652 AC XY: 4740 AN XY: 727248

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0628

Gnomad4 SAS exome AF: 0.0443

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000678

Gnomad4 OTH exome AF: 0.00957

GnomAD4 genome AF: 0.00555 AC: 845 AN: 152320 Hom.: 30 Cov.: 33 AF XY: 0.00638 AC XY: 475 AN XY: 74480

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0796

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00106 Hom.: 2

Bravo AF: 0.00431

Asia WGS AF: 0.0680 AC: 234 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.15
DANN	Benign	0.69

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: rs6281; hg19: chr4-9784889; COSMIC: COSV58577314;