9-121725216-C-T

Position:

• chr9-121725216-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001395010.1(DAB2IP):​c.362+25758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 152,234 control chromosomes in the GnomAD database, including 167 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 0.040 (167 hom., cov: 32)
• Consequence: DAB2IP NM_001395010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

Genes affected

DAB2IP (HGNC:17294): (DAB2 interacting protein) DAB2IP is a Ras (MIM 190020) GTPase-activating protein (GAP) that acts as a tumor suppressor. The DAB2IP gene is inactivated by methylation in prostate and breast cancers (Yano et al., 2005 [PubMed 15386433]).[supplied by OMIM, May 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB2IP	NM_001395010.1	c.362+25758C>T		intron_variant		ENST00000408936.8	NP_001381939.1
DAB2IP	NM_032552.4	c.278+25758C>T		intron_variant			NP_115941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB2IP	ENST00000408936.8	c.362+25758C>T		intron_variant		5	NM_001395010.1	ENSP00000386183.3
DAB2IP	ENST00000259371.7	c.278+25758C>T		intron_variant		5		ENSP00000259371.2
DAB2IP	ENST00000699487.1	c.218+24103C>T		intron_variant				ENSP00000514398.1
DAB2IP	ENST00000436835.6	n.145-31797C>T		intron_variant		3		ENSP00000409327.2

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6134 AN: 152116 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0600

Gnomad OTH AF: 0.0465

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

GnomAD4 genome AF: 0.0403 AC: 6138 AN: 152234 Hom.: 167 Cov.: 32 AF XY: 0.0386 AC XY: 2875 AN XY: 74416

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0309

Gnomad4 NFE AF: 0.0600

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0570 Hom.: 356

Bravo AF: 0.0408

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.87

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: rs13290547; hg19: chr9-124487495;