rs7991293

chr13-71580743-G-Achr13-71580743-G-C

Variant summary

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

The NM_080759.6(DACH1):c.1127-7731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,998 control chromosomes in the GnomAD database, including 2,807 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 0.13 (2807 hom., cov: 32)
• Consequence: DACH1 NM_080759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH1	NM_080759.6	c.1127-7731C>T		intron_variant		ENST00000613252.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH1	ENST00000613252.5	c.1127-7731C>T		intron_variant		1	NM_080759.6	P2
DACH1	ENST00000619232.2	c.1127-7170C>T		intron_variant		5		A2
DACH1	ENST00000706274.1	c.508-7731C>T		intron_variant
DACH1	ENST00000706275.1	c.104-7731C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19219 AN: 151880 Hom.: 2786 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.127 AC: 19285 AN: 151998 Hom.: 2807 Cov.: 32 AF XY: 0.124 AC XY: 9219 AN XY: 74302

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.0928

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.0372

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0728 Hom.: 302

Bravo AF: 0.144

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.2
Dann	Benign	0.49

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: rs7991293; hg19: chr13-72154875;