10-122568455-A-G

Variant names:

• chr10-122568455-A-G
• rs2981778
• NM_001377530.1:c.92-1707A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377530.1(DMBT1):​c.92-1707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,942 control chromosomes in the GnomAD database, including 34,513 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 0.67 (34513 hom., cov: 31)
• Consequence: DMBT1 NM_001377530.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 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.92-1707A>G		intron	N/A	NP_001364459.1	Q9UGM3-6
	DMBT1	NM_007329.3		c.92-1707A>G		intron	N/A	NP_015568.2	Q9UGM3-1
	DMBT1	NM_001320644.2		c.92-1707A>G		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.92-1707A>G		intron	N/A	ENSP00000342210.4	Q9UGM3-6
	DMBT1	ENST00000344338.7	TSL:1	c.92-1707A>G		intron	N/A	ENSP00000343175.3	Q9UGM3-3
	DMBT1	ENST00000330163.8	TSL:1	c.92-1707A>G		intron	N/A	ENSP00000327747.4	Q9UGM3-2

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101797 AN: 151824 Hom.: 34488 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.670 AC: 101862 AN: 151942 Hom.: 34513 Cov.: 31 AF XY: 0.677 AC XY: 50241 AN XY: 74254

African (AFR) AF: 0.574 AC: 23772 AN: 41436

American (AMR) AF: 0.751 AC: 11478 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2301 AN: 3468

East Asian (EAS) AF: 0.774 AC: 3980 AN: 5142

South Asian (SAS) AF: 0.747 AC: 3595 AN: 4810

European-Finnish (FIN) AF: 0.748 AC: 7893 AN: 10554

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46544 AN: 67942

Other (OTH) AF: 0.678 AC: 1429 AN: 2108

Alfa AF: 0.684 Hom.: 13802

Bravo AF: 0.670

Asia WGS AF: 0.746 AC: 2594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.53
PhyloP100		-2.3
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: rs2981778; hg19: chr10-124327971;