13-71630557-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_080759.6(DACH1):c.1125C>G(p.Val375=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,582,204 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (31 hom.)
• Consequence: DACH1 NM_080759.6 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003527
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-71630557-G-C is Benign according to our data. Variant chr13-71630557-G-C is described in ClinVar as [Benign]. Clinvar id is 774219.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.65 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00251 (382/152202) while in subpopulation AMR AF= 0.0227 (347/15268). AF 95% confidence interval is 0.0208. There are 9 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 382 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH1	NM_080759.6	c.1125C>G	p.Val375=	splice_region_variant, synonymous_variant	3/11	ENST00000613252.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH1	ENST00000613252.5	c.1125C>G	p.Val375=	splice_region_variant, synonymous_variant	3/11	1	NM_080759.6	P2
DACH1	ENST00000619232.2	c.1125C>G	p.Val375=	splice_region_variant, synonymous_variant	3/12	5		A2
DACH1	ENST00000706275.1	c.102C>G	p.Val34=	splice_region_variant, synonymous_variant	2/10
DACH1	ENST00000706274.1	c.507+51238C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 382 AN: 152084 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00493 AC: 1089 AN: 220978 Hom.: 29 AF XY: 0.00332 AC XY: 400 AN XY: 120392

Gnomad AFR exome AF: 0.000406

Gnomad AMR exome AF: 0.0404

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000185

Gnomad SAS exome AF: 0.000365

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000952

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00101 AC: 1438 AN: 1430002 Hom.: 31 Cov.: 31 AF XY: 0.000785 AC XY: 558 AN XY: 710396

Gnomad4 AFR exome AF: 0.000189

Gnomad4 AMR exome AF: 0.0366

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.000460

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000118

Gnomad4 OTH exome AF: 0.00100

GnomAD4 genome AF: 0.00251 AC: 382 AN: 152202 Hom.: 9 Cov.: 32 AF XY: 0.00300 AC XY: 223 AN XY: 74396

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.0227

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.0000467 Hom.: 0

Bravo AF: 0.00408

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.095
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000035
dbscSNV1_RF	Benign	0.062
SpliceAI score (max)		0.16		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: rs144078930; hg19: chr13-72204689;