rs75209396

Variant names:

• chr10-122570905-C-G
• rs75209396
• NM_001377530.1:c.155C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-122570905-C-G
• chr10-122570905-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001377530.1(DMBT1):​c.155C>G​(p.Ser52Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,613,340 control chromosomes in the GnomAD database, including 1,509 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.057 (776 hom., cov: 33)
  • Exomes 𝑓: 0.011 (733 hom.)
• Consequence: DMBT1 NM_001377530.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.139
• Publications: 9 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 (MetaRNN=0.0013635755).
• BP6: Variant 10-122570905-C-G is Benign according to our data. Variant chr10-122570905-C-G is described in ClinVar as Benign. ClinVar VariationId is 3037372.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 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.155C>G	p.Ser52Trp	missense	Exon 4 of 56	NP_001364459.1	Q9UGM3-6
	DMBT1	NM_007329.3		c.155C>G	p.Ser52Trp	missense	Exon 4 of 53	NP_015568.2	Q9UGM3-1
	DMBT1	NM_001320644.2		c.155C>G	p.Ser52Trp	missense	Exon 4 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.155C>G	p.Ser52Trp	missense	Exon 4 of 56	ENSP00000342210.4	Q9UGM3-6
	DMBT1	ENST00000344338.7	TSL:1	c.155C>G	p.Ser52Trp	missense	Exon 4 of 52	ENSP00000343175.3	Q9UGM3-3
	DMBT1	ENST00000330163.8	TSL:1	c.155C>G	p.Ser52Trp	missense	Exon 4 of 40	ENSP00000327747.4	Q9UGM3-2

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8701 AN: 152116 Hom.: 771 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00584

Gnomad OTH AF: 0.0460

GnomAD2 exomes AF: 0.0172 AC: 4290 AN: 249214 AF XY: 0.0140

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.00815

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000511

Gnomad NFE exome AF: 0.00567

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0106 AC: 15555 AN: 1461106 Hom.: 733 Cov.: 31 AF XY: 0.00983 AC XY: 7148 AN XY: 726904

African (AFR) AF: 0.200 AC: 6685 AN: 33458

American (AMR) AF: 0.0130 AC: 583 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00693 AC: 181 AN: 26124

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.00235 AC: 203 AN: 86244

European-Finnish (FIN) AF: 0.000693 AC: 37 AN: 53400

Middle Eastern (MID) AF: 0.0203 AC: 117 AN: 5768

European-Non Finnish (NFE) AF: 0.00598 AC: 6641 AN: 1111340

Other (OTH) AF: 0.0183 AC: 1106 AN: 60356

GnomAD4 genome AF: 0.0573 AC: 8717 AN: 152234 Hom.: 776 Cov.: 33 AF XY: 0.0559 AC XY: 4159 AN XY: 74438

African (AFR) AF: 0.188 AC: 7804 AN: 41502

American (AMR) AF: 0.0237 AC: 363 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4822

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00582 AC: 396 AN: 68024

Other (OTH) AF: 0.0455 AC: 96 AN: 2110

Alfa AF: 0.00917 Hom.: 26

Bravo AF: 0.0647

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.175 AC: 658

ESP6500EA AF: 0.00619 AC: 51

ExAC AF: 0.0198 AC: 2394

Asia WGS AF: 0.0120 AC: 42 AN: 3478

EpiCase AF: 0.00573

EpiControl AF: 0.00699

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DMBT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.14
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.089
Sift	Uncertain	0.015	D
Sift4G	Benign	0.071	T
Polyphen		0.57	P
Vest4		0.19
MPC		0.36
ClinPred		0.035	T
GERP RS		0.97
Varity_R		0.070
gMVP		0.29
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75209396; hg19: chr10-124330421;