rs75209396

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001377530.1(DMBT1):c.155C>G(p.Ser52Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,613,340 control chromosomes in the GnomAD database, including 1,509 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.057 ( 776 hom., cov: 33)

Exomes 𝑓: 0.011 ( 733 hom. )

Consequence

DMBT1
NM_001377530.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.139

Publications

9 publications found

Variant links:

Genes affected

DMBT1 (HGNC:2926): (deleted in malignant brain tumors 1) Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. This gene was originally isolated based on its deletion in a medulloblastoma cell line. This gene is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The encoded protein precursor is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system. [provided by RefSeq, Mar 2016]

DMBT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013635755).

BP6

Variant 10-122570905-C-G is Benign according to our data. Variant chr10-122570905-C-G is described in ClinVar as [Benign]. Clinvar id is 3037372.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1 link	c.155C>G	p.Ser52Trp	missense_variant	Exon 4 of 56	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10 link	c.155C>G	p.Ser52Trp	missense_variant	Exon 4 of 56	1	NM_001377530.1	ENSP00000342210.4		Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8701

AN:

152116

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00584

Gnomad OTH

AF:

0.0460

GnomAD2 exomes

AF:

0.0172

AC:

4290

AN:

249214

AF XY:

0.0140

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000511

Gnomad NFE exome

AF:

0.00567

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0106

AC:

15555

AN:

1461106

Hom.:

733

Cov.:

AF XY:

0.00983

AC XY:

7148

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.200

AC:

6685

AN:

33458

American (AMR)

AF:

0.0130

AC:

583

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00693

AC:

181

AN:

26124

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.00235

AC:

203

AN:

86244

European-Finnish (FIN)

AF:

0.000693

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0203

AC:

117

AN:

5768

European-Non Finnish (NFE)

AF:

0.00598

AC:

6641

AN:

1111340

Other (OTH)

AF:

0.0183

AC:

1106

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

816

1632

2448

3264

4080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0573

AC:

8717

AN:

152234

Hom.:

776

Cov.:

AF XY:

0.0559

AC XY:

4159

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.188

AC:

7804

AN:

41502

American (AMR)

AF:

0.0237

AC:

363

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00951

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00332

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00582

AC:

396

AN:

68024

Other (OTH)

AF:

0.0455

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

355

710

1065

1420

1775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00917

Hom.:

Bravo

AF:

0.0647

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.175

AC:

658

ESP6500EA

AF:

0.00619

AC:

ExAC

AF:

0.0198

AC:

2394

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00573

EpiControl

AF:

0.00699

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMBT1-related disorder

Benign:1

Jun 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

.;.;.;.;T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.61

T;.;.;T;.;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;N;N;N;N

PhyloP100

0.14

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.67

N;N;N;N;N;N;.

REVEL

Benign

0.089

Sift

Uncertain

0.015

D;D;D;D;D;D;.

Sift4G

Benign

0.071

T;T;D;T;T;D;T

Polyphen

0.57

P;P;P;P;D;P;D

Vest4

0.19

MPC

0.36

ClinPred

0.035

GERP RS

0.97

Varity_R

0.070

gMVP

0.29

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs75209396

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over