rs202144423

Variant names:

• chr10-122589001-G-A
• rs202144423
• NM_001377530.1:c.1841G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-122589001-G-A
• chr10-122589001-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001377530.1(DMBT1):​c.1841G>A​(p.Arg614Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,588,618 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R614L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00051 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (36 hom.)
• Consequence: DMBT1 NM_001377530.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.23

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013797164).
• BP6: Variant 10-122589001-G-A is Benign according to our data. Variant chr10-122589001-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1	c.1841G>A	p.Arg614Gln	missense_variant	Exon 17 of 56	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10	c.1841G>A	p.Arg614Gln	missense_variant	Exon 17 of 56	1	NM_001377530.1	ENSP00000342210.4

Frequencies

GnomAD3 genomes AF: 0.000511 AC: 76 AN: 148712 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000899

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00746

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000487

GnomAD2 exomes AF: 0.000437 AC: 107 AN: 244696 AF XY: 0.000400

Gnomad AFR exome AF: 0.000583

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00513

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000839

GnomAD4 exome AF: 0.000158 AC: 227 AN: 1439784 Hom.: 36 Cov.: 33 AF XY: 0.000145 AC XY: 104 AN XY: 715580

African (AFR) AF: 0.000269 AC: 9 AN: 33406

American (AMR) AF: 0.0000224 AC: 1 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.00390 AC: 148 AN: 37924

South Asian (SAS) AF: 0.0000485 AC: 4 AN: 82522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51240

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5638

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1099112

Other (OTH) AF: 0.00101 AC: 60 AN: 59450

GnomAD4 genome AF: 0.000511 AC: 76 AN: 148834 Hom.: 6 Cov.: 32 AF XY: 0.000580 AC XY: 42 AN XY: 72472

African (AFR) AF: 0.000897 AC: 37 AN: 41260

American (AMR) AF: 0.000133 AC: 2 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00748 AC: 36 AN: 4816

South Asian (SAS) AF: 0.00 AC: 0 AN: 4398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66786

Other (OTH) AF: 0.000483 AC: 1 AN: 2070

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000518

ExAC AF: 0.000342 AC: 41

EpiCase AF: 0.0000551

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	.;.;.;T;T
Eigen	Benign	0.043
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;.;T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.014	T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	4.0	H;.;.;H;H
PhyloP100		3.2
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.8	D;D;D;D;.
REVEL	Benign	0.25
Sift	Uncertain	0.016	D;D;D;D;.
Sift4G	Benign	0.077	T;T;T;T;T
Polyphen		1.0	D;D;D;D;D
Vest4		0.75
MVP		0.18
MPC		0.058
ClinPred		0.12	T
GERP RS		2.3
Varity_R		0.40
gMVP		0.59
Mutation Taster		=100/0	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs202144423; hg19: chr10-124348517;