rs11523871

Variant names:

• chr10-122570194-C-A
• rs11523871
• NM_001377530.1:c.124C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-122570194-C-A
• chr10-122570194-C-G
• chr10-122570194-C-T

Variant summary

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

The NM_001377530.1(DMBT1):​c.124C>A​(p.Pro42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,556,636 control chromosomes in the GnomAD database, including 383,520 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (36132 hom., cov: 33)
  • Exomes 𝑓: 0.70 (347388 hom.)
• Consequence: DMBT1 NM_001377530.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 31 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 (MetaRNN=1.2438222E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1	c.124C>A	p.Pro42Thr	missense_variant	Exon 3 of 56	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10	c.124C>A	p.Pro42Thr	missense_variant	Exon 3 of 56	1	NM_001377530.1	ENSP00000342210.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104427 AN: 151890 Hom.: 36103 Cov.: 33

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.685

GnomAD2 exomes AF: 0.724 AC: 180311 AN: 249142 AF XY: 0.722

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.790

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.688

Gnomad OTH exome AF: 0.717

GnomAD4 exome AF: 0.698 AC: 979787 AN: 1404628 Hom.: 347388 Cov.: 38 AF XY: 0.699 AC XY: 490074 AN XY: 701346

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.619 AC: 19954 AN: 32240

American (AMR) AF: 0.836 AC: 37274 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 16784 AN: 25740

East Asian (EAS) AF: 0.805 AC: 31710 AN: 39394

South Asian (SAS) AF: 0.737 AC: 62718 AN: 85092

European-Finnish (FIN) AF: 0.737 AC: 39245 AN: 53264

Middle Eastern (MID) AF: 0.696 AC: 3938 AN: 5660

European-Non Finnish (NFE) AF: 0.686 AC: 727710 AN: 1060306

Other (OTH) AF: 0.694 AC: 40454 AN: 58332

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.687 AC: 104499 AN: 152008 Hom.: 36132 Cov.: 33 AF XY: 0.693 AC XY: 51509 AN XY: 74304

African (AFR) AF: 0.633 AC: 26221 AN: 41434

American (AMR) AF: 0.757 AC: 11576 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2303 AN: 3472

East Asian (EAS) AF: 0.775 AC: 3984 AN: 5142

South Asian (SAS) AF: 0.750 AC: 3616 AN: 4824

European-Finnish (FIN) AF: 0.747 AC: 7906 AN: 10586

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

European-Non Finnish (NFE) AF: 0.685 AC: 46568 AN: 67944

Other (OTH) AF: 0.688 AC: 1455 AN: 2114

Alfa AF: 0.685 Hom.: 39413

Bravo AF: 0.689

TwinsUK AF: 0.682 AC: 2530

ALSPAC AF: 0.673 AC: 2594

ESP6500AA AF: 0.642 AC: 2407

ESP6500EA AF: 0.689 AC: 5666

ExAC AF: 0.716 AC: 86478

Asia WGS AF: 0.749 AC: 2606 AN: 3478

EpiCase AF: 0.690

EpiControl AF: 0.696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0010
DANN	Benign	0.40
DEOGEN2	Benign	0.020	.;.;.;.;T;.;T
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.8
FATHMM_MKL	Benign	0.00039	N
LIST_S2	Benign	0.28	T;.;.;T;.;T;T
MetaRNN	Benign	0.0000012	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N;N;N;N;N;N
PhyloP100		-3.1
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.51	N;N;N;N;N;N;.
REVEL	Benign	0.0080
Sift	Benign	0.83	T;T;T;T;T;T;.
Sift4G	Benign	0.061	T;T;T;T;T;T;T
Polyphen		0.015	B;B;B;B;B;B;B
Vest4		0.019
MPC		0.057
ClinPred		0.00026	T
GERP RS		-3.0
Varity_R		0.024
gMVP		0.29
Mutation Taster		=100/0	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: rs11523871; hg19: chr10-124329710; COSMIC: COSV107356348;