rs2078588

chr13-71727500-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_080759.6(DACH1):c.849-45590G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,070 control chromosomes in the GnomAD database, including 12,670 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 0.26 (12670 hom., cov: 32)
• Consequence: DACH1 NM_080759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

DACH1 (HGNC:2663): (dachshund family transcription factor 1) This gene encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression and cell fate determination during development. The protein contains a Ski domain that is highly conserved from Drosophila to human. Expression of this gene is lost in some forms of metastatic cancer, and is correlated with poor prognosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH1	NM_080759.6	c.849-45590G>T		intron_variant		ENST00000613252.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH1	ENST00000613252.5	c.849-45590G>T		intron_variant		1	NM_080759.6	P2
DACH1	ENST00000619232.2	c.849-45590G>T		intron_variant		5		A2
DACH1	ENST00000706274.1	c.392-45590G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39295 AN: 151950 Hom.: 12616 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.259 AC: 39406 AN: 152070 Hom.: 12670 Cov.: 32 AF XY: 0.254 AC XY: 18878 AN XY: 74358

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0720

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.0841

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0421

Gnomad4 OTH AF: 0.220

Alfa AF: 0.0696 Hom.: 1665

Bravo AF: 0.293

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	15
Dann	Benign	0.72

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: rs2078588; hg19: chr13-72301632;