1-222942767-C-T

Position:

• chr1-222942767-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377229.1(DISP1):​c.-17-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,611,098 control chromosomes in the GnomAD database, including 26,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2537 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24229 hom.)
• Consequence: DISP1 NM_001377229.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0570

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-222942767-C-T is Benign according to our data. Variant chr1-222942767-C-T is described in ClinVar as [Benign]. Clinvar id is 1247665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISP1	NM_001377229.1	c.-17-40C>T		intron_variant		ENST00000675850.1	NP_001364158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISP1	ENST00000675850.1	c.-17-40C>T		intron_variant			NM_001377229.1	ENSP00000502357.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26900 AN: 151878 Hom.: 2527 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.176 AC: 257087 AN: 1459102 Hom.: 24229 Cov.: 30 AF XY: 0.174 AC XY: 126445 AN XY: 726012

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0905

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.177 AC: 26930 AN: 151996 Hom.: 2537 Cov.: 31 AF XY: 0.174 AC XY: 12895 AN XY: 74302

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.170

Alfa AF: 0.144 Hom.: 399

Bravo AF: 0.176

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.63

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: rs75109669; hg19: chr1-223116109;