NM_194247.4:c.*1707C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194247.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA3	NM_194247.4	MANE Select	c.*1707C>T		3_prime_UTR	Exon 11 of 11	NP_919223.1
	HNRNPA3	NM_001330247.2		c.*1707C>T		3_prime_UTR	Exon 11 of 11	NP_001317176.1
	HNRNPA3	NM_001330251.2		c.*1707C>T		3_prime_UTR	Exon 10 of 10	NP_001317180.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA3	ENST00000392524.7	TSL:5 MANE Select	c.*1707C>T		3_prime_UTR	Exon 11 of 11	ENSP00000376309.2
	HNRNPA3	ENST00000861956.1		c.*1707C>T		3_prime_UTR	Exon 11 of 11	ENSP00000532015.1
	HNRNPA3	ENST00000925137.1		c.*1707C>T		3_prime_UTR	Exon 11 of 11	ENSP00000595196.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.746 AC: 315 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.434 AC: 17995 AN: 41446

American (AMR) AF: 0.795 AC: 12150 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2846 AN: 3470

East Asian (EAS) AF: 0.749 AC: 3879 AN: 5178

South Asian (SAS) AF: 0.837 AC: 4039 AN: 4824

European-Finnish (FIN) AF: 0.751 AC: 7938 AN: 10566

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54499 AN: 68002

Other (OTH) AF: 0.735 AC: 1552 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.8
DANN	Benign	0.68
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8470; hg19: chr2-178085827;