Genetic Variant DMBT1:c.-93T>C (chr10-122560678-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000344338.7(DMBT1):c.-93T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 952,796 control chromosomes in the GnomAD database, including 236,889 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 0.68 ( 35239 hom., cov: 31)

Exomes 𝑓: 0.71 ( 201650 hom. )

Consequence

DMBT1
ENST00000344338.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.566

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1 link	c.-93T>C		upstream_gene_variant		ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10 link	c.-93T>C		upstream_gene_variant		1	NM_001377530.1	ENSP00000342210.4		Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.678

AC:

102927

AN:

151874

Hom.:

35212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.733

Gnomad AMR

AF:

0.755

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.685

GnomAD4 exome

AF:

0.708

AC:

566896

AN:

800804

Hom.:

201650

Cov.:

AF XY:

0.710

AC XY:

292108

AN XY:

411308

show subpopulations

African (AFR)

AF:

0.575

AC:

10670

AN:

18570

American (AMR)

AF:

0.816

AC:

19524

AN:

23938

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

13427

AN:

19142

East Asian (EAS)

AF:

0.794

AC:

25474

AN:

32102

South Asian (SAS)

AF:

0.777

AC:

43003

AN:

55324

European-Finnish (FIN)

AF:

0.738

AC:

34226

AN:

46396

Middle Eastern (MID)

AF:

0.737

AC:

3243

AN:

4400

European-Non Finnish (NFE)

AF:

0.694

AC:

391067

AN:

563538

Other (OTH)

AF:

0.702

AC:

26262

AN:

37394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7989

15979

23968

31958

39947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7460

14920

22380

29840

37300

<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:

0.678

AC:

102989

AN:

151992

Hom.:

35239

Cov.:

AF XY:

0.684

AC XY:

50809

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.586

AC:

24262

AN:

41398

American (AMR)

AF:

0.756

AC:

11550

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

2457

AN:

3470

East Asian (EAS)

AF:

0.757

AC:

3908

AN:

5160

South Asian (SAS)

AF:

0.783

AC:

3762

AN:

4802

European-Finnish (FIN)

AF:

0.748

AC:

7899

AN:

10566

Middle Eastern (MID)

AF:

0.714

AC:

210

AN:

294

European-Non Finnish (NFE)

AF:

0.689

AC:

46817

AN:

67994

Other (OTH)

AF:

0.689

AC:

1457

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1666

3332

4998

6664

8330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.676

Hom.:

7927

Bravo

AF:

0.676

Asia WGS

AF:

0.759

AC:

2639

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.57

PromoterAI

0.030

Neutral

(source)

Mutation Taster

=300/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over