rs2981804

Variant names:

• chr10-122574140-G-A
• rs2981804
• NM_001377530.1:c.283+378G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377530.1(DMBT1):​c.283+378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,044 control chromosomes in the GnomAD database, including 18,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (18491 hom., cov: 33)
• Consequence: DMBT1 NM_001377530.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.675
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-122574140-G-A is Benign according to our data. Variant chr10-122574140-G-A is described in ClinVar as Benign. ClinVar VariationId is 1225238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377530.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	NM_001377530.1	MANE Select	c.283+378G>A		intron	N/A	NP_001364459.1	Q9UGM3-6
	DMBT1	NM_007329.3		c.283+378G>A		intron	N/A	NP_015568.2	Q9UGM3-1
	DMBT1	NM_001320644.2		c.283+378G>A		intron	N/A	NP_001307573.1	A0A590UJ76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	ENST00000338354.10	TSL:1 MANE Select	c.283+378G>A		intron	N/A	ENSP00000342210.4	Q9UGM3-6
	DMBT1	ENST00000344338.7	TSL:1	c.283+378G>A		intron	N/A	ENSP00000343175.3	Q9UGM3-3
	DMBT1	ENST00000330163.8	TSL:1	c.283+378G>A		intron	N/A	ENSP00000327747.4	Q9UGM3-2

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73086 AN: 151926 Hom.: 18473 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.481 AC: 73136 AN: 152044 Hom.: 18491 Cov.: 33 AF XY: 0.483 AC XY: 35881 AN XY: 74322

African (AFR) AF: 0.324 AC: 13427 AN: 41484

American (AMR) AF: 0.607 AC: 9272 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1734 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1906 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1771 AN: 4816

European-Finnish (FIN) AF: 0.600 AC: 6342 AN: 10572

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36975 AN: 67950

Other (OTH) AF: 0.504 AC: 1065 AN: 2114

Alfa AF: 0.511 Hom.: 5055

Bravo AF: 0.481

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.66
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2981804; hg19: chr10-124333656;