rs41292890

Variant names:

• chr6-154039520-C-T
• rs41292890
• ENST00000434900.6:c.255C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-154039520-C-T
• chr6-154039520-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001145279.4(OPRM1):​c.255C>T​(p.Ser85Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,594,948 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (12 hom.)
• Consequence: OPRM1 NM_001145279.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -1.47
• Publications: 3 publications found

Genes affected

OPRM1 (HGNC:8156): (opioid receptor mu 1) This gene encodes one of at least three opioid receptors in humans; the mu opioid receptor (MOR). The MOR is the principal target of endogenous opioid peptides and opioid analgesic agents such as beta-endorphin and enkephalins. The MOR also has an important role in dependence to other drugs of abuse, such as nicotine, cocaine, and alcohol via its modulation of the dopamine system. The NM_001008503.2:c.118A>G allele has been associated with opioid and alcohol addiction and variations in pain sensitivity but evidence for it having a causal role is conflicting. Multiple transcript variants encoding different isoforms have been found for this gene. Though the canonical MOR belongs to the superfamily of 7-transmembrane-spanning G-protein-coupled receptors some isoforms of this gene have only 6 transmembrane domains. [provided by RefSeq, Oct 2013]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 6-154039520-C-T is Benign according to our data. Variant chr6-154039520-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 829269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145279.4. 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
	OPRM1	NM_000914.5	MANE Select	c.-25C>T		5_prime_UTR	Exon 1 of 4	NP_000905.3	P35372-1
	OPRM1	NM_001145279.4		c.255C>T	p.Ser85Ser	synonymous	Exon 3 of 6	NP_001138751.1	P35372-10
	OPRM1	NM_001285524.1		c.255C>T	p.Ser85Ser	synonymous	Exon 2 of 5	NP_001272453.1	P35372-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRM1	ENST00000434900.6	TSL:1	c.255C>T	p.Ser85Ser	synonymous	Exon 3 of 6	ENSP00000394624.2	P35372-10
	OPRM1	ENST00000360422.8	TSL:1	c.162C>T	p.Ser54Ser	synonymous	Exon 1 of 4	ENSP00000353598.5	L0E130
	OPRM1	ENST00000520282.5	TSL:1	c.120C>T	p.Ser40Ser	synonymous	Exon 2 of 3	ENSP00000430247.1	E7EW71

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 434 AN: 152226 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00312

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00351 AC: 757 AN: 215878 AF XY: 0.00350

Gnomad AFR exome AF: 0.000648

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.0138

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00378

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.00447

GnomAD4 exome AF: 0.00376 AC: 5425 AN: 1442606 Hom.: 12 Cov.: 31 AF XY: 0.00367 AC XY: 2629 AN XY: 715728

African (AFR) AF: 0.000754 AC: 25 AN: 33170

American (AMR) AF: 0.00274 AC: 114 AN: 41576

Ashkenazi Jewish (ASJ) AF: 0.0143 AC: 365 AN: 25558

East Asian (EAS) AF: 0.0000516 AC: 2 AN: 38794

South Asian (SAS) AF: 0.00261 AC: 217 AN: 83280

European-Finnish (FIN) AF: 0.00338 AC: 175 AN: 51838

Middle Eastern (MID) AF: 0.00956 AC: 55 AN: 5754

European-Non Finnish (NFE) AF: 0.00381 AC: 4205 AN: 1103004

Other (OTH) AF: 0.00448 AC: 267 AN: 59632

GnomAD4 genome AF: 0.00284 AC: 433 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.00278 AC XY: 207 AN XY: 74488

African (AFR) AF: 0.000625 AC: 26 AN: 41592

American (AMR) AF: 0.00438 AC: 67 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00312 AC: 212 AN: 68028

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00322 Hom.: 1

Bravo AF: 0.00300

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.20
DANN	Benign	0.87
PhyloP100		-1.5
PromoterAI		0.0010	Neutral
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: rs41292890; hg19: chr6-154360655;