rs10492537

Variant names:

• chr13-71844162-T-C
• rs10492537
• NM_080759.6:c.848+21760A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080759.6(DACH1):​c.848+21760A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 152,280 control chromosomes in the GnomAD database, including 340 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 0.064 (340 hom., cov: 32)
• Consequence: DACH1 NM_080759.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.934
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080759.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACH1	NM_080759.6	MANE Select	c.848+21760A>G		intron	N/A	NP_542937.3
	DACH1	NM_001366712.1		c.848+21760A>G		intron	N/A	NP_001353641.1
	DACH1	NM_080760.6		c.848+21760A>G		intron	N/A	NP_542938.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACH1	ENST00000613252.5	TSL:1 MANE Select	c.848+21760A>G		intron	N/A	ENSP00000482245.1
	DACH1	ENST00000619232.2	TSL:5	c.848+21760A>G		intron	N/A	ENSP00000482797.1
	DACH1	ENST00000706274.1		c.389+21760A>G		intron	N/A	ENSP00000516320.1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9685 AN: 152162 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0649

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

GnomAD4 genome AF: 0.0637 AC: 9700 AN: 152280 Hom.: 340 Cov.: 32 AF XY: 0.0638 AC XY: 4751 AN XY: 74460

African (AFR) AF: 0.0843 AC: 3501 AN: 41550

American (AMR) AF: 0.0520 AC: 795 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3470

East Asian (EAS) AF: 0.105 AC: 546 AN: 5182

South Asian (SAS) AF: 0.0679 AC: 328 AN: 4832

European-Finnish (FIN) AF: 0.0380 AC: 403 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0544 AC: 3697 AN: 68012

Other (OTH) AF: 0.0662 AC: 140 AN: 2116

Alfa AF: 0.0575 Hom.: 165

Bravo AF: 0.0661

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.70
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10492537; hg19: chr13-72418294;