rs10507796

Positions:

• chr13-71653498-G-A

Variant summary

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

The NM_080759.6(DACH1):​c.965-22781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 152,290 control chromosomes in the GnomAD database, including 120 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 0.010 (120 hom., cov: 32)
• Consequence: DACH1 NM_080759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH1	NM_080759.6	c.965-22781C>T		intron_variant		ENST00000613252.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH1	ENST00000613252.5	c.965-22781C>T		intron_variant		1	NM_080759.6	P2
DACH1	ENST00000619232.2	c.965-22781C>T		intron_variant		5		A2
DACH1	ENST00000706274.1	c.507+28297C>T		intron_variant
DACH1	ENST00000706275.1	c.-60+21452C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1522 AN: 152172 Hom.: 119 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.0100 AC: 1524 AN: 152290 Hom.: 120 Cov.: 32 AF XY: 0.0114 AC XY: 852 AN XY: 74472

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00418 Hom.: 4

Bravo AF: 0.0112

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.45

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: rs10507796; hg19: chr13-72227630;