8-104347204-C-T

Variant names:

• chr8-104347204-C-T
• rs2458413
• NM_030788.4:c.-12-1337C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030788.4(DCSTAMP):​c.-12-1337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,002 control chromosomes in the GnomAD database, including 16,440 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 0.44 (16440 hom., cov: 33)
• Consequence: DCSTAMP NM_030788.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 28 publications found

Genes affected

DCSTAMP (HGNC:18549): (dendrocyte expressed seven transmembrane protein) This gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells. The encoded protein is involved in a range of immunological functions carried out by dendritic cells. This protein plays a role in osteoclastogenesis and myeloid differentiation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

DPYS (HGNC:3013): (dihydropyrimidinase) Dihydropyrimidinase catalyzes the conversion of 5,6-dihydrouracil to 3-ureidopropionate in pyrimidine metabolism. Dihydropyrimidinase is expressed at a high level in liver and kidney as a major 2.5-kb transcript and a minor 3.8-kb transcript. Defects in the DPYS gene are linked to dihydropyrimidinuria. [provided by RefSeq, Jul 2008]

DPYS Gene-Disease associations (from GenCC):

• dihydropyrimidinuria

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030788.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCSTAMP	NM_030788.4	MANE Select	c.-12-1337C>T		intron	N/A	NP_110415.1
	DCSTAMP	NM_001257317.1		c.-12-1337C>T		intron	N/A	NP_001244246.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCSTAMP	ENST00000297581.2	TSL:1 MANE Select	c.-12-1337C>T		intron	N/A	ENSP00000297581.2
	DCSTAMP	ENST00000622554.1	TSL:5	c.-12-1337C>T		intron	N/A	ENSP00000480546.1
	DCSTAMP	ENST00000517364.1	TSL:2	n.330-1337C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66337 AN: 151882 Hom.: 16445 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 66348 AN: 152002 Hom.: 16440 Cov.: 33 AF XY: 0.435 AC XY: 32324 AN XY: 74314

African (AFR) AF: 0.217 AC: 9002 AN: 41440

American (AMR) AF: 0.361 AC: 5506 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2076 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1111 AN: 5182

South Asian (SAS) AF: 0.496 AC: 2390 AN: 4816

European-Finnish (FIN) AF: 0.542 AC: 5714 AN: 10544

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38893 AN: 67976

Other (OTH) AF: 0.458 AC: 965 AN: 2106

Alfa AF: 0.533 Hom.: 97309

Bravo AF: 0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.32
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: rs2458413; hg19: chr8-105359432;