rs2706112

Variant names:

• chr2-177225133-G-A
• rs2706112
• ENST00000677863.2:c.*5741G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-177225133-G-A
• chr2-177225133-G-C

Variant summary

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

The ENST00000677863.2(HNRNPA3):​c.*5741G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,114 control chromosomes in the GnomAD database, including 38,826 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 0.70 (38826 hom., cov: 34)
• Consequence: HNRNPA3 ENST00000677863.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 4 publications found

Genes affected

HNRNPA3 (HGNC:24941): (heterogeneous nuclear ribonucleoprotein A3) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

NFE2L2 Gene-Disease associations (from GenCC):

• immunodeficiency, developmental delay, and hypohomocysteinemia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000677863.2	c.*5741G>A		3_prime_UTR_variant	Exon 10 of 10			ENSP00000504218.1
NFE2L2	ENST00000699342.1	c.715-2501C>T		intron_variant	Intron 5 of 6			ENSP00000514317.1
NFE2L2	ENST00000699404.1	c.712-2501C>T		intron_variant	Intron 9 of 10			ENSP00000514365.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105745 AN: 151998 Hom.: 38816 Cov.: 34

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.733

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.695 AC: 105772 AN: 152114 Hom.: 38826 Cov.: 34 AF XY: 0.697 AC XY: 51833 AN XY: 74374

African (AFR) AF: 0.434 AC: 17987 AN: 41448

American (AMR) AF: 0.795 AC: 12157 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2847 AN: 3470

East Asian (EAS) AF: 0.749 AC: 3875 AN: 5176

South Asian (SAS) AF: 0.836 AC: 4043 AN: 4834

European-Finnish (FIN) AF: 0.750 AC: 7931 AN: 10574

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54441 AN: 68008

Other (OTH) AF: 0.734 AC: 1550 AN: 2112

Alfa AF: 0.745 Hom.: 5402

Bravo AF: 0.687

Asia WGS AF: 0.758 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.71
DANN	Benign	0.51
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs2706112; hg19: chr2-178089861;