4-9781804-G-C

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.-226G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 422,328 control chromosomes in the GnomAD database, including 182,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (64649 hom., cov: 33)
  • Exomes 𝑓: 0.93 (118048 hom.)
• Consequence: DRD5 NM_000798.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.97

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=-0.92).
• BP6: Variant 4-9781804-G-C is Benign according to our data. Variant chr4-9781804-G-C is described in ClinVar as [Benign]. Clinvar id is 1243205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRD5	NM_000798.5	c.-226G>C		5_prime_UTR_variant	1/1	ENST00000304374.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRD5	ENST00000304374.4	c.-226G>C		5_prime_UTR_variant	1/1		NM_000798.5	P1
SLC2A9	ENST00000503803.5	n.386-1739C>G		intron_variant, non_coding_transcript_variant		3
SLC2A9	ENST00000508585.5	n.182-10435C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139959 AN: 152152 Hom.: 64595 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.927

GnomAD4 exome AF: 0.933 AC: 252054 AN: 270058 Hom.: 118048 Cov.: 3 AF XY: 0.934 AC XY: 127871 AN XY: 136872

Gnomad4 AFR exome AF: 0.872

Gnomad4 AMR exome AF: 0.877

Gnomad4 ASJ exome AF: 0.941

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.830

Gnomad4 FIN exome AF: 0.965

Gnomad4 NFE exome AF: 0.956

Gnomad4 OTH exome AF: 0.933

GnomAD4 genome AF: 0.920 AC: 140067 AN: 152270 Hom.: 64649 Cov.: 33 AF XY: 0.918 AC XY: 68366 AN XY: 74456

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.942

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.965

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.929

Alfa AF: 0.924 Hom.: 3088

Bravo AF: 0.913

Asia WGS AF: 0.823 AC: 2860 AN: 3472

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.0
Dann	Benign	0.52

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: rs2076907; hg19: chr4-9783428;