1-186401149-C-T

Variant names:

• chr1-186401149-C-T
• rs180959681
• NM_017847.6:c.1000+2105C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017847.6(ODR4):​c.1000+2105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,443,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ODR4 NM_017847.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 7 publications found

Genes affected

ODR4 (HGNC:24299): (odr-4 GPCR localization factor homolog) Predicted to be involved in protein localization. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110991806).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017847.6. 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
	ODR4	NM_017847.6	MANE Select	c.1000+2105C>T		intron	N/A	NP_060317.3
	ODR4	NM_001164245.2		c.931+2105C>T		intron	N/A	NP_001157717.1	Q5SWX8-2
	ODR4	NM_001164246.2		c.904+2105C>T		intron	N/A	NP_001157718.1	Q5SWX8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODR4	ENST00000287859.11	TSL:1 MANE Select	c.1000+2105C>T		intron	N/A	ENSP00000287859.6	Q5SWX8-1
	ODR4	ENST00000367470.8	TSL:5	c.931+2105C>T		intron	N/A	ENSP00000356440.3	Q5SWX8-2
	ODR4	ENST00000419367.8	TSL:2	c.904+2105C>T		intron	N/A	ENSP00000395084.3	Q5SWX8-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1443588 Hom.: 0 Cov.: 28 AF XY: 0.00000557 AC XY: 4 AN XY: 717496

African (AFR) AF: 0.00 AC: 0 AN: 33120

American (AMR) AF: 0.00 AC: 0 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.00 AC: 0 AN: 39204

South Asian (SAS) AF: 0.00 AC: 0 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00000546 AC: 6 AN: 1098460

Other (OTH) AF: 0.0000169 AC: 1 AN: 59290

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	0.0027	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	0.35
DANN	Benign	0.86
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.0027	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.11	T
PhyloP100		-0.92
Sift4G	Pathogenic	0.0	D
Polyphen		0.0040	B
Vest4		0.36
MVP		0.095
MPC		0.55
GERP RS		-1.4
Varity_R		0.035
gMVP		0.21
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs180959681; hg19: chr1-186370281;