rs7383

Variant names:

• chr10-122643591-T-C
• rs7383
• NM_001377530.1:c.*193T>C

Variant summary

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

The NM_001377530.1(DMBT1):​c.*193T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 765,614 control chromosomes in the GnomAD database, including 92,355 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 (25687 hom., cov: 32)
  • Exomes 𝑓: 0.45 (66668 hom.)
• Consequence: DMBT1 NM_001377530.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.813 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	NM_001377530.1	MANE Select	c.*193T>C		3_prime_UTR	Exon 56 of 56	NP_001364459.1
	DMBT1	NM_007329.3		c.*193T>C		3_prime_UTR	Exon 53 of 53	NP_015568.2
	DMBT1	NM_001320644.2		c.*193T>C		3_prime_UTR	Exon 53 of 53	NP_001307573.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	ENST00000338354.10	TSL:1 MANE Select	c.*193T>C		3_prime_UTR	Exon 56 of 56	ENSP00000342210.4
	DMBT1	ENST00000344338.7	TSL:1	c.*193T>C		3_prime_UTR	Exon 52 of 52	ENSP00000343175.3
	DMBT1	ENST00000330163.8	TSL:1	c.*193T>C		3_prime_UTR	Exon 40 of 40	ENSP00000327747.4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84022 AN: 151864 Hom.: 25644 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.449 AC: 275764 AN: 613632 Hom.: 66668 Cov.: 8 AF XY: 0.454 AC XY: 142481 AN XY: 313628

African (AFR) AF: 0.823 AC: 12567 AN: 15264

American (AMR) AF: 0.534 AC: 10053 AN: 18836

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 6722 AN: 14550

East Asian (EAS) AF: 0.671 AC: 21084 AN: 31420

South Asian (SAS) AF: 0.614 AC: 29474 AN: 48002

European-Finnish (FIN) AF: 0.394 AC: 11555 AN: 29318

Middle Eastern (MID) AF: 0.522 AC: 1199 AN: 2296

European-Non Finnish (NFE) AF: 0.399 AC: 168506 AN: 422754

Other (OTH) AF: 0.468 AC: 14604 AN: 31192

GnomAD4 genome AF: 0.554 AC: 84129 AN: 151982 Hom.: 25687 Cov.: 32 AF XY: 0.555 AC XY: 41227 AN XY: 74268

African (AFR) AF: 0.820 AC: 34004 AN: 41464

American (AMR) AF: 0.536 AC: 8182 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1662 AN: 3466

East Asian (EAS) AF: 0.675 AC: 3471 AN: 5144

South Asian (SAS) AF: 0.623 AC: 2994 AN: 4804

European-Finnish (FIN) AF: 0.400 AC: 4214 AN: 10546

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28018 AN: 67966

Other (OTH) AF: 0.519 AC: 1097 AN: 2112

Alfa AF: 0.469 Hom.: 8292

Bravo AF: 0.576

Asia WGS AF: 0.653 AC: 2270 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	0.95
DANN	Benign	0.51
PhyloP100		-0.27
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: rs7383; hg19: chr10-124403107;