chr17-48046570-T-C

Variant names:

• chr17-48046570-T-C
• rs3764400
• ENST00000578660.3:n.2035A>G

Variant summary

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

The ENST00000578660.3(NFE2L1-DT):​n.2035A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,200 control chromosomes in the GnomAD database, including 1,560 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 0.12 (1560 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFE2L1-DT ENST00000578660.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520
• Publications: 28 publications found

Genes affected

NFE2L1-DT (HGNC:54812): (NFE2L1 divergent transcript)

COPZ2 (HGNC:19356): (COPI coat complex subunit zeta 2) This gene encodes a member of the adaptor complexes small subunit family. The encoded protein is a subunit of the coatomer protein complex, a seven-subunit complex that functions in the formation of COPI-type, non-clathrin-coated vesicles. COPI vesicles function in the retrograde Golgi-to-ER transport of dilysine-tagged proteins. [provided by RefSeq, Feb 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPZ2	XM_047436209.1	c.-25+639A>G		intron_variant	Intron 1 of 7		XP_047292165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L1-DT	ENST00000578660.3	n.2035A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18097 AN: 152082 Hom.: 1559 Cov.: 32

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.113

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.119 AC: 18104 AN: 152200 Hom.: 1560 Cov.: 32 AF XY: 0.123 AC XY: 9145 AN XY: 74412

African (AFR) AF: 0.0336 AC: 1397 AN: 41546

American (AMR) AF: 0.0854 AC: 1306 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2154 AN: 5172

South Asian (SAS) AF: 0.151 AC: 726 AN: 4816

European-Finnish (FIN) AF: 0.208 AC: 2205 AN: 10586

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9405 AN: 67996

Other (OTH) AF: 0.115 AC: 244 AN: 2116

Alfa AF: 0.131 Hom.: 4160

Bravo AF: 0.107

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.54
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs3764400; hg19: chr17-46123932;