chr2-177220409-G-A

Position:

• chr2-177220409-G-A

Variant summary

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

The NM_194247.4(HNRNPA3):​c.*1017G>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 0.678 in 154,376 control chromosomes in the GnomAD database, including 38,339 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 0.68 (37680 hom., cov: 32)
  • Exomes 𝑓: 0.75 (659 hom.)
• Consequence: HNRNPA3 NM_194247.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940

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]

HNRNPA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• 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/exons	MANE	Protein	UniProt
HNRNPA3	NM_194247.4	c.*1017G>A		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.*1017G>A		3_prime_UTR_variant	11/11	5	NM_194247.4	ENSP00000376309.2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102876 AN: 151954 Hom.: 37669 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.752 AC: 1732 AN: 2304 Hom.: 659 Cov.: 0 AF XY: 0.766 AC XY: 902 AN XY: 1178

Gnomad4 AFR exome AF: 0.355

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.925

Gnomad4 FIN exome AF: 0.746

Gnomad4 NFE exome AF: 0.736

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.677 AC: 102896 AN: 152072 Hom.: 37680 Cov.: 32 AF XY: 0.679 AC XY: 50493 AN XY: 74360

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.787

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: 0.719

Alfa AF: 0.723 Hom.: 5381

Bravo AF: 0.665

Asia WGS AF: 0.755 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9068; hg19: chr2-178085137; COSMIC: COSV66820705; COSMIC: COSV66820705;