rs1967551

Variant names:

• chr4-9783510-T-C
• rs1967551
• NM_000798.5:c.*47T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-9783510-T-C
• chr4-9783510-T-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000798.5(DRD5):​c.*47T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,525,428 control chromosomes in the GnomAD database, including 287,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.55 (23725 hom., cov: 32)
  • Exomes 𝑓: 0.61 (263645 hom.)
• Consequence: DRD5 NM_000798.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.0160
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• hypouricemia, renal, 2

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-9783510-T-C is Benign according to our data. Variant chr4-9783510-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1287057.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000798.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	NM_000798.5	MANE Select	c.*47T>C		3_prime_UTR	Exon 1 of 1	NP_000789.1	P21918

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	ENST00000304374.4	TSL:6 MANE Select	c.*47T>C		3_prime_UTR	Exon 1 of 1	ENSP00000306129.2	P21918
	DRD5	ENST00000888644.1		c.*47T>C		3_prime_UTR	Exon 2 of 2	ENSP00000558703.1
	DRD5	ENST00000953045.1		c.*47T>C		3_prime_UTR	Exon 2 of 2	ENSP00000623104.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 83023 AN: 151944 Hom.: 23712 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.545

GnomAD2 exomes AF: 0.564 AC: 107520 AN: 190510 AF XY: 0.570

Gnomad AFR exome AF: 0.397

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.695

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.646

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.615 AC: 844278 AN: 1373366 Hom.: 263645 Cov.: 23 AF XY: 0.612 AC XY: 414116 AN XY: 676768

African (AFR) AF: 0.384 AC: 11948 AN: 31112

American (AMR) AF: 0.532 AC: 19336 AN: 36336

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 14795 AN: 21608

East Asian (EAS) AF: 0.364 AC: 14167 AN: 38944

South Asian (SAS) AF: 0.467 AC: 34344 AN: 73530

European-Finnish (FIN) AF: 0.615 AC: 30670 AN: 49902

Middle Eastern (MID) AF: 0.599 AC: 3126 AN: 5218

European-Non Finnish (NFE) AF: 0.644 AC: 682647 AN: 1060044

Other (OTH) AF: 0.587 AC: 33245 AN: 56672

GnomAD4 genome AF: 0.546 AC: 83058 AN: 152062 Hom.: 23725 Cov.: 32 AF XY: 0.543 AC XY: 40386 AN XY: 74330

African (AFR) AF: 0.396 AC: 16426 AN: 41452

American (AMR) AF: 0.552 AC: 8444 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3472

East Asian (EAS) AF: 0.335 AC: 1722 AN: 5146

South Asian (SAS) AF: 0.465 AC: 2240 AN: 4822

European-Finnish (FIN) AF: 0.605 AC: 6396 AN: 10572

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43617 AN: 68000

Other (OTH) AF: 0.546 AC: 1154 AN: 2112

Alfa AF: 0.588 Hom.: 7939

Bravo AF: 0.537

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	Hereditary attention deficit-hyperactivity disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.29
PhyloP100		-0.016
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1967551; hg19: chr4-9785134; COSMIC: COSV58577284;