rs1975285

Variant names:

• chr8-56446123-G-C
• rs1975285
• NM_001135690.3:c.-3-167C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-56446123-G-C
• chr8-56446123-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135690.3(PENK):​c.-3-167C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 732,162 control chromosomes in the GnomAD database, including 232,902 homozygotes. 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: 𝑓 0.83 (52190 hom., cov: 33)
  • Exomes 𝑓: 0.79 (180712 hom.)
• Consequence: PENK NM_001135690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 6 publications found

Genes affected

PENK (HGNC:8831): (proenkephalin) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the pentapeptide opioids Met-enkephalin and Leu-enkephalin, which are stored in synaptic vesicles, then released into the synapse where they bind to mu- and delta-opioid receptors to modulate the perception of pain. Other non-opioid cleavage products may function in distinct biological activities. [provided by RefSeq, Jul 2015]

PENK-AS1 (HGNC:55519): (PENK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135690.3. 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
	PENK	NM_001135690.3	MANE Select	c.-3-167C>G		intron	N/A	NP_001129162.1	P01210
	PENK-AS1	NR_125813.1		n.317G>C		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PENK	ENST00000451791.7	TSL:1 MANE Select	c.-3-167C>G		intron	N/A	ENSP00000400894.2	P01210
	PENK	ENST00000961478.1		c.-3-167C>G		intron	N/A	ENSP00000631537.1
	PENK	ENST00000961479.1		c.-3-167C>G		intron	N/A	ENSP00000631538.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125427 AN: 152048 Hom.: 52134 Cov.: 33

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.788 AC: 456906 AN: 579996 Hom.: 180712 Cov.: 8 AF XY: 0.789 AC XY: 233614 AN XY: 296048

African (AFR) AF: 0.931 AC: 13270 AN: 14248

American (AMR) AF: 0.849 AC: 15552 AN: 18328

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 11288 AN: 14036

East Asian (EAS) AF: 0.870 AC: 26953 AN: 30968

South Asian (SAS) AF: 0.847 AC: 36938 AN: 43636

European-Finnish (FIN) AF: 0.804 AC: 30155 AN: 37516

Middle Eastern (MID) AF: 0.793 AC: 1725 AN: 2176

European-Non Finnish (NFE) AF: 0.764 AC: 297367 AN: 389298

Other (OTH) AF: 0.794 AC: 23658 AN: 29790

GnomAD4 genome AF: 0.825 AC: 125545 AN: 152166 Hom.: 52190 Cov.: 33 AF XY: 0.825 AC XY: 61389 AN XY: 74378

African (AFR) AF: 0.928 AC: 38562 AN: 41564

American (AMR) AF: 0.826 AC: 12643 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2767 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4460 AN: 5128

South Asian (SAS) AF: 0.849 AC: 4097 AN: 4828

European-Finnish (FIN) AF: 0.801 AC: 8479 AN: 10582

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51831 AN: 67972

Other (OTH) AF: 0.820 AC: 1734 AN: 2114

Alfa AF: 0.801 Hom.: 6107

Bravo AF: 0.831

Asia WGS AF: 0.883 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.38
PhyloP100		-0.22
PromoterAI		-0.048	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1975285; hg19: chr8-57358682;