Variant chr10-122643428-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377530.1(DMBT1):c.*30G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,589,632 control chromosomes in the GnomAD database, including 40,226 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 0.26 ( 5422 hom., cov: 31)

Exomes 𝑓: 0.22 ( 34804 hom. )

Consequence

DMBT1
NM_001377530.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.86

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMBT1	NM_001377530.1 linkuse as main transcript	c.*30G>A		3_prime_UTR_variant	56/56	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10 linkuse as main transcript	c.*30G>A		3_prime_UTR_variant	56/56	1	NM_001377530.1	ENSP00000342210	P4	Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

38940

AN:

151746

Hom.:

5427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.219

AC:

46543

AN:

212104

Hom.:

5287

AF XY:

0.213

AC XY:

24521

AN XY:

114896

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.160

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.217

AC:

312226

AN:

1437768

Hom.:

34804

Cov.:

AF XY:

0.215

AC XY:

152871

AN XY:

712374

show subpopulations

Gnomad4 AFR exome

AF:

0.373

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.256

AC:

38950

AN:

151864

Hom.:

5422

Cov.:

AF XY:

0.253

AC XY:

18804

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.235

Hom.:

2009

Bravo

AF:

0.268

Asia WGS

AF:

0.167

AC:

582

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.15

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over