6-71301998-C-A

Position:

• chr6-71301998-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024576.5(OGFRL1):​c.1305C>A​(p.Asp435Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OGFRL1 NM_024576.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071258366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OGFRL1	NM_024576.5	c.1305C>A	p.Asp435Glu	missense_variant	7/7	ENST00000370435.5
LOC124901339	XR_007059640.1	n.5781+8298G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGFRL1	ENST00000370435.5	c.1305C>A	p.Asp435Glu	missense_variant	7/7	1	NM_024576.5	P1
LINC00472	ENST00000710850.1	n.355-68341G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2023

The c.1305C>A (p.D435E) alteration is located in exon 7 (coding exon 7) of the OGFRL1 gene. This alteration results from a C to A substitution at nucleotide position 1305, causing the aspartic acid (D) at amino acid position 435 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0069	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.66	N;.
REVEL	Benign	0.051
Sift	Uncertain	0.0090	D;.
Sift4G	Benign	0.68	T;.
Polyphen		0.0080	B;.
Vest4		0.059
MutPred		0.13		Gain of solvent accessibility (P = 0.1751);.;
MVP		0.23
MPC		0.26
ClinPred		0.21	T
GERP RS		0.88
Varity_R		0.064
gMVP		0.043

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

Publications

LitVar

Other links and lift over

dbSNP: rs1766413620; hg19: chr6-72011701;