Genetic Variant DMBT1:p.Pro2464Pro (chr10-122643161-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001377530.1(DMBT1):c.7392A>G(p.Pro2464Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,613,560 control chromosomes in the GnomAD database, including 179,724 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 0.55 ( 25600 hom., cov: 31)

Exomes 𝑓: 0.45 ( 154124 hom. )

Consequence

DMBT1
NM_001377530.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -7.74

Publications

16 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP7

Synonymous conserved (PhyloP=-7.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1 link	c.7392A>G	p.Pro2464Pro	synonymous_variant	Exon 56 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.7392A>G	p.Pro2464Pro	synonymous_variant	Exon 56 of 56	1	NM_001377530.1	ENSP00000342210.4		Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

83874

AN:

151768

Hom.:

25557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.818

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.519

GnomAD2 exomes

AF:

0.511

AC:

127491

AN:

249250

AF XY:

0.506

show subpopulations

Gnomad AFR exome

AF:

0.827

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.449

AC:

656404

AN:

1461674

Hom.:

154124

Cov.:

AF XY:

0.453

AC XY:

329113

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.835

AC:

27948

AN:

33480

American (AMR)

AF:

0.560

AC:

25034

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

12267

AN:

26134

East Asian (EAS)

AF:

0.674

AC:

26744

AN:

39700

South Asian (SAS)

AF:

0.618

AC:

53300

AN:

86258

European-Finnish (FIN)

AF:

0.396

AC:

21132

AN:

53400

Middle Eastern (MID)

AF:

0.528

AC:

3047

AN:

5766

European-Non Finnish (NFE)

AF:

0.412

AC:

458365

AN:

1111842

Other (OTH)

AF:

0.473

AC:

28567

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

22484

44967

67451

89934

112418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14494

28988

43482

57976

72470

<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:

0.553

AC:

83981

AN:

151886

Hom.:

25600

Cov.:

AF XY:

0.555

AC XY:

41140

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.818

AC:

33916

AN:

41458

American (AMR)

AF:

0.536

AC:

8181

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

1659

AN:

3468

East Asian (EAS)

AF:

0.675

AC:

3469

AN:

5138

South Asian (SAS)

AF:

0.623

AC:

2989

AN:

4800

European-Finnish (FIN)

AF:

0.400

AC:

4207

AN:

10518

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.412

AC:

27974

AN:

67918

Other (OTH)

AF:

0.520

AC:

1098

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1678

3357

5035

6714

8392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.461

Hom.:

19913

Bravo

AF:

0.575

EpiCase

AF:

0.420

EpiControl

AF:

0.426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.033

(source)

DANN

Benign

0.34

PhyloP100

-7.7

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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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