rs8470

Variant names:

• chr2-177221099-C-T
• rs8470
• NM_194247.4:c.*1707C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_194247.4(HNRNPA3):​c.*1707C>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 0.696 in 152,518 control chromosomes in the GnomAD database, including 39,005 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 (38887 hom., cov: 33)
  • Exomes 𝑓: 0.75 (118 hom.)
• Consequence: HNRNPA3 NM_194247.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA3	NM_194247.4	c.*1707C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000392524.7	NP_919223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000392524.7	c.*1707C>T		3_prime_UTR_variant	Exon 11 of 11	5	NM_194247.4	ENSP00000376309.2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105798 AN: 151972 Hom.: 38872 Cov.: 33

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.734

GnomAD4 exome AF: 0.748 AC: 320 AN: 428 Hom.: 118 Cov.: 0 AF XY: 0.748 AC XY: 193 AN XY: 258

Gnomad4 FIN exome AF: 0.746

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.696 AC: 105837 AN: 152090 Hom.: 38887 Cov.: 33 AF XY: 0.698 AC XY: 51872 AN XY: 74360

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.735

Alfa AF: 0.755 Hom.: 6951

Bravo AF: 0.687

Asia WGS AF: 0.761 AC: 2649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.8
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8470; hg19: chr2-178085827;