NM_001377229.1:c.-17-40C>T

Variant names:

• chr1-222942767-C-T
• rs75109669
• NM_001377229.1:c.-17-40C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 VariationId 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.

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.-17-40C>T		intron	N/A	NP_001364158.1	Q96F81
	DISP1	NM_001369594.1		c.-17-40C>T		intron	N/A	NP_001356523.1	Q96F81
	DISP1	NM_001377228.1		c.-17-40C>T		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.-17-40C>T		intron	N/A	ENSP00000502357.1	Q96F81
	DISP1	ENST00000284476.7	TSL:1	c.-17-40C>T		intron	N/A	ENSP00000284476.6	Q96F81
	DISP1	ENST00000482856.1	TSL:1	n.131-40C>T		intron	N/A

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

African (AFR) AF: 0.201 AC: 6721 AN: 33422

American (AMR) AF: 0.0898 AC: 4014 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4546 AN: 26122

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39688

South Asian (SAS) AF: 0.0905 AC: 7778 AN: 85932

European-Finnish (FIN) AF: 0.177 AC: 9476 AN: 53408

Middle Eastern (MID) AF: 0.167 AC: 961 AN: 5762

European-Non Finnish (NFE) AF: 0.193 AC: 213833 AN: 1109758

Other (OTH) AF: 0.162 AC: 9742 AN: 60300

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

African (AFR) AF: 0.196 AC: 8127 AN: 41444

American (AMR) AF: 0.133 AC: 2028 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 626 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5174

South Asian (SAS) AF: 0.0744 AC: 358 AN: 4810

European-Finnish (FIN) AF: 0.175 AC: 1849 AN: 10546

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13335 AN: 67966

Other (OTH) AF: 0.170 AC: 360 AN: 2112

Alfa AF: 0.168 Hom.: 1077

Bravo AF: 0.176

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

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: rs75109669; hg19: chr1-223116109;