rs9441941

chr1-223005219-A-Cchr1-223005219-A-Gchr1-223005219-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377229.1(DISP1):c.3822A>C(p.Pro1274=) 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:4

Conservation

PhyloP100: -0.900

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DISP1	NM_001377229.1 linkuse as main transcript	c.3822A>C	p.Pro1274=	synonymous_variant	9/9	ENST00000675850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP1	ENST00000675850.1 linkuse as main transcript	c.3822A>C	p.Pro1274=	synonymous_variant	9/9		NM_001377229.1	P1

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

GnomAD3 exomes

AF:

0.547

AC:

137015

AN:

250608

Hom.:

37727

AF XY:

0.545

AC XY:

73801

AN XY:

135454

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 SAS exome

AF:

0.476

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

Gnomad4 AFR exome

AF:

0.447

Gnomad4 AMR exome

AF:

0.542

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.510

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.595

Gnomad4 NFE exome

AF:

0.577

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.535

AC:

81278

AN:

152046

Hom.:

21985

Cov.:

AF XY:

0.534

AC XY:

39715

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.451

Gnomad4 AMR

AF:

0.549

Gnomad4 ASJ

AF:

0.567

Gnomad4 EAS

AF:

0.495

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.582

Gnomad4 OTH

AF:

0.536

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 28, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.82

Dann

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over