rs626277

Positions:

• chr13-71773564-A-C
• chr13-71773564-A-G
• chr13-71773564-A-T

Variant summary

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

The NM_080759.6(DACH1):​c.849-91654T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,726 control chromosomes in the GnomAD database, including 21,183 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 0.51 (21183 hom., cov: 33)
• Consequence: DACH1 NM_080759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACH1	NM_080759.6	c.849-91654T>G		intron_variant		ENST00000613252.5	NP_542937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACH1	ENST00000613252.5	c.849-91654T>G		intron_variant		1	NM_080759.6	ENSP00000482245	P2
DACH1	ENST00000619232.2	c.849-91654T>G		intron_variant		5		ENSP00000482797	A2
DACH1	ENST00000706274.1	c.392-91654T>G		intron_variant				ENSP00000516320

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77325 AN: 151608 Hom.: 21133 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.510 AC: 77434 AN: 151726 Hom.: 21183 Cov.: 33 AF XY: 0.518 AC XY: 38391 AN XY: 74150

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.488

Alfa AF: 0.428 Hom.: 22255

Bravo AF: 0.525

Asia WGS AF: 0.727 AC: 2519 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.79

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: rs626277; hg19: chr13-72347696;