NM_001377229.1:c.-17-279G>A

Variant names:

• chr1-222942528-G-A
• rs116787287
• NM_001377229.1:c.-17-279G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001377229.1(DISP1):​c.-17-279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 152,000 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.012 (30 hom., cov: 31)
• Consequence: DISP1 NM_001377229.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.54
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-222942528-G-A is Benign according to our data. Variant chr1-222942528-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1218757.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1764/152000) while in subpopulation AFR AF = 0.0409 (1695/41430). AF 95% confidence interval is 0.0393. There are 30 homozygotes in GnomAd4. There are 816 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR,AD,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377229.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISP1	NM_001377229.1	MANE Select	c.-17-279G>A		intron	N/A	NP_001364158.1	Q96F81
	DISP1	NM_001369594.1		c.-17-279G>A		intron	N/A	NP_001356523.1	Q96F81
	DISP1	NM_001377228.1		c.-17-279G>A		intron	N/A	NP_001364157.1	Q96F81

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISP1	ENST00000675850.1	MANE Select	c.-17-279G>A		intron	N/A	ENSP00000502357.1	Q96F81
	DISP1	ENST00000284476.7	TSL:1	c.-17-279G>A		intron	N/A	ENSP00000284476.6	Q96F81
	DISP1	ENST00000482856.1	TSL:1	n.131-279G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1760 AN: 151884 Hom.: 30 Cov.: 31

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00766

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0116 AC: 1764 AN: 152000 Hom.: 30 Cov.: 31 AF XY: 0.0110 AC XY: 816 AN XY: 74286

African (AFR) AF: 0.0409 AC: 1695 AN: 41430

American (AMR) AF: 0.00256 AC: 39 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67972

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00874 Hom.: 1

Bravo AF: 0.0132

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.35
PhyloP100		-2.5
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

Other links and lift over

dbSNP: rs116787287; hg19: chr1-223115870;