chr6-71289016-C-A

Variant names:

• chr6-71289016-C-A
• rs867388532
• NM_024576.5:c.80C>A

Variant summary

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

The NM_024576.5(OGFRL1):​c.80C>A​(p.Ser27*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000821 in 1,217,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 8.2e-7 (0 hom.)
• Consequence: OGFRL1 NM_024576.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 0 publications found

Genes affected

OGFRL1 (HGNC:21378): (opioid growth factor receptor like 1) Predicted to enable opioid growth factor receptor activity. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LINC00472 (HGNC:21380): (long intergenic non-protein coding RNA 472)

LOC124901339 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024576.5. 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
	OGFRL1	NM_024576.5	MANE Select	c.80C>A	p.Ser27*	stop_gained	Exon 1 of 7	NP_078852.3
	OGFRL1	NM_001324266.2		c.80C>A	p.Ser27*	stop_gained	Exon 1 of 7	NP_001311195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGFRL1	ENST00000370435.5	TSL:1 MANE Select	c.80C>A	p.Ser27*	stop_gained	Exon 1 of 7	ENSP00000359464.3	Q5TC84
	LINC00472	ENST00000412751.5	TSL:3	n.106-11702G>T		intron	N/A
	LINC00472	ENST00000423255.5	TSL:3	n.46-4076G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.21e-7 AC: 1 AN: 1217738 Hom.: 0 Cov.: 29 AF XY: 0.00000165 AC XY: 1 AN XY: 604548

⚠️ 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: 24516

American (AMR) AF: 0.00 AC: 0 AN: 30552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18462

East Asian (EAS) AF: 0.0000437 AC: 1 AN: 22866

South Asian (SAS) AF: 0.00 AC: 0 AN: 67240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4392

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 975818

Other (OTH) AF: 0.00 AC: 0 AN: 45666

⚠️ 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
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.50	D
PhyloP100		4.0
Vest4		0.088
GERP RS		1.1
PromoterAI		-0.022	Neutral
Mutation Taster		=14/186	disease causing (fs/PTC)

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: rs867388532; hg19: chr6-71998719;