rs2296498

chr13-94443857-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001922.5(DCT):c.1180-220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,138 control chromosomes in the GnomAD database, including 1,604 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 0.14 (1604 hom., cov: 32)
• Consequence: DCT NM_001922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972

Genes affected

DCT (HGNC:2709): (dopachrome tautomerase) Predicted to enable dopachrome isomerase activity. Involved in response to blue light. Located in intracellular membrane-bounded organelle and plasma membrane. Implicated in oculocutaneous albinism. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCT	NM_001922.5	c.1180-220T>C		intron_variant		ENST00000377028.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCT	ENST00000377028.10	c.1180-220T>C		intron_variant		1	NM_001922.5	P1
DCT	ENST00000446125.1	c.1279-220T>C		intron_variant		1
DCT	ENST00000483392.6	c.*55-220T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21207 AN: 152020 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.140 AC: 21238 AN: 152138 Hom.: 1604 Cov.: 32 AF XY: 0.139 AC XY: 10373 AN XY: 74380

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0952

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.147

Alfa AF: 0.129 Hom.: 160

Bravo AF: 0.138

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.98
Dann	Benign	0.32

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: rs2296498; hg19: chr13-95096111;