1-186401059-C-T

Variant names:

• chr1-186401059-C-T
• rs757077225
• NM_017847.6:c.1000+2015C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017847.6(ODR4):​c.1000+2015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,443,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ODR4 NM_017847.6 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.644
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05830592).

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+2015C>T		intron	N/A	NP_060317.3
	ODR4	NM_001164245.2		c.931+2015C>T		intron	N/A	NP_001157717.1	Q5SWX8-2
	ODR4	NM_001164246.2		c.904+2015C>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+2015C>T		intron	N/A	ENSP00000287859.6	Q5SWX8-1
	ODR4	ENST00000367470.8	TSL:5	c.931+2015C>T		intron	N/A	ENSP00000356440.3	Q5SWX8-2
	ODR4	ENST00000419367.8	TSL:2	c.904+2015C>T		intron	N/A	ENSP00000395084.3	Q5SWX8-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248516 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1443802 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 717168

African (AFR) AF: 0.00 AC: 0 AN: 33174

American (AMR) AF: 0.00 AC: 0 AN: 44008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25522

East Asian (EAS) AF: 0.00 AC: 0 AN: 39142

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1099190

Other (OTH) AF: 0.00 AC: 0 AN: 59238

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.39
DANN	Benign	0.78
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.0080	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.058	T
PhyloP100		-0.64
Sift4G	Pathogenic	0.0	D
Polyphen		0.0030	B
Vest4		0.21
MVP		0.095
MPC		0.64
GERP RS		-2.5
Varity_R		0.034
gMVP		0.13
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: rs757077225; hg19: chr1-186370191;