10-122560678-T-C

Position:

• chr10-122560678-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000344338(DMBT1):​c.-93T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 952,796 control chromosomes in the GnomAD database, including 236,889 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 0.68 (35239 hom., cov: 31)
  • Exomes 𝑓: 0.71 (201650 hom.)
• Consequence: DMBT1 ENST00000344338 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.122560678T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000344338	c.-93T>C		5_prime_UTR_variant	1/52	1		ENSP00000343175.3
DMBT1	ENST00000330163	c.-93T>C		5_prime_UTR_variant	1/40	1		ENSP00000327747.4
DMBT1	ENST00000368909	c.-93T>C		5_prime_UTR_variant	1/53	5		ENSP00000357905.3

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102927 AN: 151874 Hom.: 35212 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.685

GnomAD4 exome AF: 0.708 AC: 566896 AN: 800804 Hom.: 201650 Cov.: 10 AF XY: 0.710 AC XY: 292108 AN XY: 411308

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.701

Gnomad4 EAS exome AF: 0.794

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.694

Gnomad4 OTH exome AF: 0.702

GnomAD4 genome AF: 0.678 AC: 102989 AN: 151992 Hom.: 35239 Cov.: 31 AF XY: 0.684 AC XY: 50809 AN XY: 74288

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.689

Alfa AF: 0.678 Hom.: 7798

Bravo AF: 0.676

Asia WGS AF: 0.759 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.63

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: rs2981745; hg19: chr10-124320194;