rs1052715

Variant names:

• chr10-122643161-A-G
• rs1052715
• NM_001377530.1:c.7392A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-122643161-A-G
• chr10-122643161-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.74
• Publications: 16 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 -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.

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.7392A>G	p.Pro2464Pro	synonymous	Exon 56 of 56	NP_001364459.1	Q9UGM3-6
	DMBT1	NM_007329.3		c.7005A>G	p.Pro2335Pro	synonymous	Exon 53 of 53	NP_015568.2	Q9UGM3-1
	DMBT1	NM_001320644.2		c.7002A>G	p.Pro2334Pro	synonymous	Exon 53 of 53	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.7392A>G	p.Pro2464Pro	synonymous	Exon 56 of 56	ENSP00000342210.4	Q9UGM3-6
	DMBT1	ENST00000344338.7	TSL:1	c.6975A>G	p.Pro2325Pro	synonymous	Exon 52 of 52	ENSP00000343175.3	Q9UGM3-3
	DMBT1	ENST00000330163.8	TSL:1	c.5121A>G	p.Pro1707Pro	synonymous	Exon 40 of 40	ENSP00000327747.4	Q9UGM3-2

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

GnomAD2 exomes AF: 0.511 AC: 127491 AN: 249250 AF XY: 0.506

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

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

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.033
DANN	Benign	0.34
PhyloP100		-7.7
Mutation Taster		=97/3	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: rs1052715; hg19: chr10-124402677; COSMIC: COSV107356545;