NM_003204.3:c.147C>T

Variant names:

• chr17-48051265-C-T
• rs34230500
• NM_003204.3:c.147C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003204.3(NFE2L1):​c.147C>T​(p.Ala49Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,144 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (16 hom.)
• Consequence: NFE2L1 NM_003204.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.66
• Publications: 3 publications found

Genes affected

NFE2L1 (HGNC:7781): (NFE2 like bZIP transcription factor 1) This gene encodes a protein that is involved in globin gene expression in erythrocytes. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene, NFE2L1, and for "nuclear respiratory factor 1" which has an official symbol of NRF1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-48051265-C-T is Benign according to our data. Variant chr17-48051265-C-T is described in ClinVar as Benign. ClinVar VariationId is 785572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00738 (1123/152252) while in subpopulation AFR AF = 0.0257 (1066/41530). AF 95% confidence interval is 0.0244. There are 17 homozygotes in GnomAd4. There are 510 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1123 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003204.3. 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
	NFE2L1	NM_003204.3	MANE Select	c.147C>T	p.Ala49Ala	synonymous	Exon 2 of 6	NP_003195.1	Q14494-1
	NFE2L1	NM_001439152.1		c.147C>T	p.Ala49Ala	synonymous	Exon 2 of 6	NP_001426081.1
	NFE2L1	NM_001330261.2		c.147C>T	p.Ala49Ala	synonymous	Exon 2 of 6	NP_001317190.1	J9JIE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L1	ENST00000362042.8	TSL:1 MANE Select	c.147C>T	p.Ala49Ala	synonymous	Exon 2 of 6	ENSP00000354855.3	Q14494-1
	NFE2L1	ENST00000357480.9	TSL:1	c.147C>T	p.Ala49Ala	synonymous	Exon 2 of 5	ENSP00000350072.5	Q14494-2
	NFE2L1	ENST00000585291.5	TSL:1	c.147C>T	p.Ala49Ala	synonymous	Exon 3 of 6	ENSP00000461960.1	Q14494-2

Frequencies

GnomAD3 genomes AF: 0.00738 AC: 1122 AN: 152134 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00202 AC: 509 AN: 251488 AF XY: 0.00141

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000755 AC: 1104 AN: 1461892 Hom.: 16 Cov.: 32 AF XY: 0.000650 AC XY: 473 AN XY: 727248

African (AFR) AF: 0.0245 AC: 820 AN: 33480

American (AMR) AF: 0.00159 AC: 71 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000638 AC: 71 AN: 1112012

Other (OTH) AF: 0.00220 AC: 133 AN: 60396

GnomAD4 genome AF: 0.00738 AC: 1123 AN: 152252 Hom.: 17 Cov.: 32 AF XY: 0.00685 AC XY: 510 AN XY: 74440

African (AFR) AF: 0.0257 AC: 1066 AN: 41530

American (AMR) AF: 0.00301 AC: 46 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68016

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00577 Hom.: 11

Bravo AF: 0.00830

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		1.7
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: rs34230500; hg19: chr17-46128627;