rs17476063

Variant names:

• chr1-222843064-T-A
• rs17476063
• NM_001377229.1:c.-159+27986T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377229.1(DISP1):​c.-159+27986T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,954 control chromosomes in the GnomAD database, including 3,596 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3596 hom., cov: 32)
• Consequence: DISP1 NM_001377229.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 5 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: AR, AD, SD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP1	NM_001377229.1	c.-159+27986T>A		intron_variant	Intron 1 of 8	ENST00000675850.1	NP_001364158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP1	ENST00000675850.1	c.-159+27986T>A		intron_variant	Intron 1 of 8		NM_001377229.1	ENSP00000502357.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31477 AN: 151836 Hom.: 3588 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.207 AC: 31500 AN: 151954 Hom.: 3596 Cov.: 32 AF XY: 0.210 AC XY: 15594 AN XY: 74264

African (AFR) AF: 0.163 AC: 6785 AN: 41502

American (AMR) AF: 0.154 AC: 2353 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3468

East Asian (EAS) AF: 0.0462 AC: 239 AN: 5178

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4824

European-Finnish (FIN) AF: 0.336 AC: 3548 AN: 10568

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15956 AN: 67822

Other (OTH) AF: 0.185 AC: 389 AN: 2104

Alfa AF: 0.233 Hom.: 577

Bravo AF: 0.190

Asia WGS AF: 0.133 AC: 460 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17476063; hg19: chr1-223016406;