rs1052715

chr10-122643161-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001377530.1(DMBT1):c.7392A>G(p.Pro2464=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.74

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DMBT1	NM_001377530.1	c.7392A>G	p.Pro2464=	synonymous_variant	56/56	ENST00000338354.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMBT1	ENST00000338354.10	c.7392A>G	p.Pro2464=	synonymous_variant	56/56	1	NM_001377530.1	P4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83874 AN: 151768 Hom.: 25557 Cov.: 31

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

GnomAD3 exomes AF: 0.511 AC: 127491 AN: 249250 Hom.: 34805 AF XY: 0.506 AC XY: 68468 AN XY: 135210

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 SAS exome AF: 0.622

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.: 68 AF XY: 0.453 AC XY: 329113 AN XY: 727120

Gnomad4 AFR exome AF: 0.835

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.674

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.553 AC: 83981 AN: 151886 Hom.: 25600 Cov.: 31 AF XY: 0.555 AC XY: 41140 AN XY: 74170

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.520

Alfa AF: 0.459 Hom.: 18425

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
Dann	Benign	0.34

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

Other links and lift over

dbSNP: rs1052715; hg19: chr10-124402677;