rs757077225

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-186401059-C-A
• chr1-186401059-C-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+2015C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,802 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: 6.9e-7 (0 hom.)
• Consequence: ODR4 NM_017847.6 intron
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.18149713).

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443802 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 717168

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.00 AC: 0 AN: 1099190

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.31
DANN	Benign	0.72
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.18	T
PhyloP100		-0.64
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.28
MVP		0.076
MPC		0.64
GERP RS		-2.5
Varity_R		0.027
gMVP		0.15
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: rs757077225; hg19: chr1-186370191;