2-177222437-G-T

Position:

• chr2-177222437-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194247.4(HNRNPA3):​c.*3045G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,224 control chromosomes in the GnomAD database, including 63,123 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 0.91 (63123 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: HNRNPA3 NM_194247.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPA3	NM_194247.4	c.*3045G>T		3_prime_UTR_variant	11/11	ENST00000392524.7	NP_919223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000392524.7	c.*3045G>T		3_prime_UTR_variant	11/11	5	NM_194247.4	ENSP00000376309

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138410 AN: 152106 Hom.: 63069 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.916

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.910 AC: 138524 AN: 152224 Hom.: 63123 Cov.: 32 AF XY: 0.907 AC XY: 67495 AN XY: 74416

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.917

Alfa AF: 0.918 Hom.: 15586

Bravo AF: 0.915

Asia WGS AF: 0.854 AC: 2973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2588882; hg19: chr2-178087165;