Genetic Variant NM_001377229.1:c.890-14T>C (chr1-222994871-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377229.1(DISP1):c.890-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,572,070 control chromosomes in the GnomAD database, including 84,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9733 hom., cov: 32)

Exomes 𝑓: 0.32 ( 74706 hom. )

Consequence

DISP1
NM_001377229.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0770

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-222994871-T-C is Benign according to our data. Variant chr1-222994871-T-C is described in ClinVar as [Benign]. Clinvar id is 262132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP1	NM_001377229.1 link	c.890-14T>C		intron_variant	Intron 7 of 8	ENST00000675850.1	NP_001364158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP1	ENST00000675850.1 link	c.890-14T>C		intron_variant	Intron 7 of 8		NM_001377229.1	ENSP00000502357.1		Q96F81

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53280

AN:

151808

Hom.:

9713

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.344

AC:

85707

AN:

249154

Hom.:

15358

AF XY:

0.347

AC XY:

46815

AN XY:

134788

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.375

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.300

Gnomad SAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.319

AC:

452437

AN:

1420144

Hom.:

74706

Cov.:

AF XY:

0.322

AC XY:

228138

AN XY:

709418

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.282

Gnomad4 SAS exome

AF:

0.451

Gnomad4 FIN exome

AF:

0.356

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.351

AC:

53346

AN:

151926

Hom.:

9733

Cov.:

AF XY:

0.355

AC XY:

26383

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.296

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.376

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.253

Hom.:

1265

Bravo

AF:

0.352

Asia WGS

AF:

0.408

AC:

1419

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 20, 2019

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.77

CADD

Benign

6.9

DANN

Benign

0.84

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

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