rs9441941

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377229.1(DISP1):c.3822A>C(p.Pro1274Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,613,862 control chromosomes in the GnomAD database, including 256,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21985 hom., cov: 33)

Exomes 𝑓: 0.57 ( 234767 hom. )

Consequence

DISP1
NM_001377229.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.900

Publications

17 publications found

Variant links:

Genes affected

DISP1 (HGNC:19711): (dispatched RND transporter family member 1) The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized production of secreted protein signals. Cells surrounding the source of a particular signal respond in a graded manner according to the effective concentration of the signal, and this response produces the pattern of cell types constituting the mature structure. A novel segment-polarity gene known as dispatched has been identified in Drosophila and its protein product is required for normal Hedgehog (Hh) signaling. This gene is one of two human homologs of Drosophila dispatched and, based on sequence identity to its mouse counterpart, the encoded protein may play an essential role in Hh patterning activities in the early embryo. [provided by RefSeq, Jul 2008]

DISP1 Gene-Disease associations (from GenCC):

holoprosencephaly
Inheritance: AR, AD, SD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Illumina

DISP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-223005219-A-C is Benign according to our data. Variant chr1-223005219-A-C is described in ClinVar as [Benign]. Clinvar id is 262131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP1	NM_001377229.1 link	c.3822A>C	p.Pro1274Pro	synonymous_variant	Exon 9 of 9	ENST00000675850.1	NP_001364158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP1	ENST00000675850.1 link	c.3822A>C	p.Pro1274Pro	synonymous_variant	Exon 9 of 9		NM_001377229.1	ENSP00000502357.1		Q96F81

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81238

AN:

151930

Hom.:

21985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.437

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.471

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.540

GnomAD2 exomes

AF:

0.547

AC:

137015

AN:

250608

AF XY:

0.545

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.513

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.577

Gnomad OTH exome

AF:

0.567

GnomAD4 exome

AF:

0.565

AC:

826142

AN:

1461816

Hom.:

234767

Cov.:

AF XY:

0.563

AC XY:

409262

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.447

AC:

14980

AN:

33480

American (AMR)

AF:

0.542

AC:

24234

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

14550

AN:

26136

East Asian (EAS)

AF:

0.510

AC:

20264

AN:

39700

South Asian (SAS)

AF:

0.476

AC:

41044

AN:

86258

European-Finnish (FIN)

AF:

0.595

AC:

31768

AN:

53358

Middle Eastern (MID)

AF:

0.599

AC:

3454

AN:

5768

European-Non Finnish (NFE)

AF:

0.577

AC:

642008

AN:

1111996

Other (OTH)

AF:

0.560

AC:

33840

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

27522

55045

82567

110090

137612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17654

35308

52962

70616

88270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.535

AC:

81278

AN:

152046

Hom.:

21985

Cov.:

AF XY:

0.534

AC XY:

39715

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.451

AC:

18705

AN:

41484

American (AMR)

AF:

0.549

AC:

8397

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

1967

AN:

3472

East Asian (EAS)

AF:

0.495

AC:

2547

AN:

5148

South Asian (SAS)

AF:

0.471

AC:

2269

AN:

4822

European-Finnish (FIN)

AF:

0.584

AC:

6165

AN:

10552

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.582

AC:

39529

AN:

67964

Other (OTH)

AF:

0.536

AC:

1133

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1928

3857

5785

7714

9642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.537

Hom.:

9125

Bravo

AF:

0.528

Asia WGS

AF:

0.465

AC:

1619

AN:

3478

EpiCase

AF:

0.577

EpiControl

AF:

0.571

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.82

(source)

DANN

Benign

0.53

PhyloP100

-0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over