13-71600221-C-T

Position:

• chr13-71600221-C-T

Variant summary

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

The NM_080759.6(DACH1):​c.1127-27209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,108 control chromosomes in the GnomAD database, including 1,537 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 0.11 (1537 hom., cov: 32)
• Consequence: DACH1 NM_080759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DACH1	NM_080759.6	c.1127-27209G>A		intron_variant		ENST00000613252.5	NP_542937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACH1	ENST00000613252.5	c.1127-27209G>A		intron_variant		1	NM_080759.6	ENSP00000482245	P2
DACH1	ENST00000619232.2	c.1127-26648G>A		intron_variant		5		ENSP00000482797	A2
DACH1	ENST00000706274.1	c.508-27209G>A		intron_variant				ENSP00000516320
DACH1	ENST00000706275.1	c.104-27209G>A		intron_variant				ENSP00000516321

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16008 AN: 151990 Hom.: 1531 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.0738

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.105 AC: 16028 AN: 152108 Hom.: 1537 Cov.: 32 AF XY: 0.115 AC XY: 8535 AN XY: 74352

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.0966

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0827

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0914 Hom.: 783

Bravo AF: 0.105

Asia WGS AF: 0.379 AC: 1317 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.53
DANN	Benign	0.46

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: rs9919839; hg19: chr13-72174353;