10-122643591-T-C

Position:

• chr10-122643591-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMBT1	NM_001377530.1	c.*193T>C		3_prime_UTR_variant	56/56	ENST00000338354.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMBT1	ENST00000338354.10	c.*193T>C		3_prime_UTR_variant	56/56	1	NM_001377530.1	P4

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

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.671

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.468

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

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.519

Alfa AF: 0.464 Hom.: 6798

Bravo AF: 0.576

Asia WGS AF: 0.653 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.95
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs7383; hg19: chr10-124403107;