rs2277244

Variant names:

Variant summary

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

The NM_001377530.1(DMBT1):c.3250C>T(p.His1084Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0339 in 1,613,808 control chromosomes in the GnomAD database, including 1,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.027 ( 85 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1172 hom. )

Consequence

DMBT1
NM_001377530.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.34

Publications

11 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=0.0030488968).

BP6

Variant 10-122599067-C-T is Benign according to our data. Variant chr10-122599067-C-T is described in ClinVar as [Benign]. Clinvar id is 3037168.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1 link	c.3250C>T	p.His1084Tyr	missense_variant	Exon 26 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.3250C>T	p.His1084Tyr	missense_variant	Exon 26 of 56	1	NM_001377530.1	ENSP00000342210.4		Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4124

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00760

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0305

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.0692

Gnomad SAS

AF:

0.0806

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0308

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0401

AC:

9987

AN:

249032

AF XY:

0.0426

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.0434

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0793

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0370

GnomAD4 exome

AF:

0.0346

AC:

50546

AN:

1461530

Hom.:

1172

Cov.:

AF XY:

0.0358

AC XY:

26009

AN XY:

727054

show subpopulations

African (AFR)

AF:

0.00612

AC:

205

AN:

33472

American (AMR)

AF:

0.0422

AC:

1887

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

519

AN:

26132

East Asian (EAS)

AF:

0.0910

AC:

3612

AN:

39700

South Asian (SAS)

AF:

0.0759

AC:

6544

AN:

86250

European-Finnish (FIN)

AF:

0.0340

AC:

1817

AN:

53402

Middle Eastern (MID)

AF:

0.0519

AC:

299

AN:

5762

European-Non Finnish (NFE)

AF:

0.0302

AC:

33630

AN:

1111738

Other (OTH)

AF:

0.0337

AC:

2033

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4168

8336

12505

16673

20841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1366

2732

4098

5464

6830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0272

AC:

4135

AN:

152278

Hom.:

Cov.:

AF XY:

0.0284

AC XY:

2113

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00758

AC:

315

AN:

41560

American (AMR)

AF:

0.0307

AC:

470

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3470

East Asian (EAS)

AF:

0.0689

AC:

357

AN:

5178

South Asian (SAS)

AF:

0.0819

AC:

395

AN:

4824

European-Finnish (FIN)

AF:

0.0296

AC:

314

AN:

10604

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0308

AC:

2098

AN:

68018

Other (OTH)

AF:

0.0299

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

212

424

636

848

1060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0263

Hom.:

Bravo

AF:

0.0258

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0296

AC:

114

ESP6500AA

AF:

0.00911

AC:

ESP6500EA

AF:

0.0290

AC:

240

ExAC

AF:

0.0410

AC:

4955

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

EpiCase

AF:

0.0335

EpiControl

AF:

0.0299

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMBT1-related disorder

Benign:1

May 21, 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

Pathogenic

0.72

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

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

Eigen

Uncertain

0.42

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

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

MetaRNN

Benign

0.0030

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

MetaSVM

Benign

-0.68

MutationAssessor

Pathogenic

3.6

H;.;.;.;H;.;H

PhyloP100

4.3

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.1

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

REVEL

Uncertain

0.36

Sift

Uncertain

0.0050

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

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D

Vest4

0.30

MPC

0.058

ClinPred

0.091

GERP RS

3.6

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.69

gMVP

0.21

Mutation Taster

=70/30

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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