rs8441

Variant names:

• chr10-122643428-G-A
• rs8441
• NM_001377530.1:c.*30G>A

Variant summary

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

The NM_001377530.1(DMBT1):​c.*30G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,589,632 control chromosomes in the GnomAD database, including 40,226 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 0.26 (5422 hom., cov: 31)
  • Exomes 𝑓: 0.22 (34804 hom.)
• Consequence: DMBT1 NM_001377530.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.86
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1	c.*30G>A		3_prime_UTR_variant	Exon 56 of 56	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10	c.*30G>A		3_prime_UTR_variant	Exon 56 of 56	1	NM_001377530.1	ENSP00000342210.4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38940 AN: 151746 Hom.: 5427 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.237

GnomAD2 exomes AF: 0.219 AC: 46543 AN: 212104 AF XY: 0.213

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.160

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.217 AC: 312226 AN: 1437768 Hom.: 34804 Cov.: 34 AF XY: 0.215 AC XY: 152871 AN XY: 712374

African (AFR) AF: 0.373 AC: 12257 AN: 32844

American (AMR) AF: 0.210 AC: 8734 AN: 41496

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 7254 AN: 25638

East Asian (EAS) AF: 0.164 AC: 6321 AN: 38498

South Asian (SAS) AF: 0.144 AC: 12055 AN: 83706

European-Finnish (FIN) AF: 0.193 AC: 10004 AN: 51962

Middle Eastern (MID) AF: 0.249 AC: 1289 AN: 5182

European-Non Finnish (NFE) AF: 0.219 AC: 241094 AN: 1098932

Other (OTH) AF: 0.222 AC: 13218 AN: 59510

GnomAD4 genome AF: 0.256 AC: 38950 AN: 151864 Hom.: 5422 Cov.: 31 AF XY: 0.253 AC XY: 18804 AN XY: 74230

African (AFR) AF: 0.368 AC: 15236 AN: 41396

American (AMR) AF: 0.244 AC: 3724 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3468

East Asian (EAS) AF: 0.149 AC: 765 AN: 5148

South Asian (SAS) AF: 0.132 AC: 629 AN: 4762

European-Finnish (FIN) AF: 0.192 AC: 2030 AN: 10578

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14891 AN: 67934

Other (OTH) AF: 0.235 AC: 494 AN: 2106

Alfa AF: 0.236 Hom.: 2364

Bravo AF: 0.268

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.61
PhyloP100		-3.9
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: rs8441; hg19: chr10-124402944; COSMIC: COSV57547996;