chr2-177220409-G-A

Variant names:

• chr2-177220409-G-A
• rs9068
• NM_194247.4:c.*1017G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 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.*1017G>A		3_prime_UTR	Exon 11 of 11	NP_919223.1
	HNRNPA3	NR_138470.2		n.2160G>A		non_coding_transcript_exon	Exon 11 of 12
	HNRNPA3	NM_001330247.2		c.*1017G>A		3_prime_UTR	Exon 11 of 11	NP_001317176.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA3	ENST00000392524.7	TSL:5 MANE Select	c.*1017G>A		3_prime_UTR	Exon 11 of 11	ENSP00000376309.2
	HNRNPA3	ENST00000483137.2	TSL:2	n.2695G>A		non_coding_transcript_exon	Exon 8 of 9
	HNRNPA3	ENST00000676488.1		n.*1017G>A		non_coding_transcript_exon	Exon 10 of 11	ENSP00000503067.1

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

African (AFR) AF: 0.355 AC: 22 AN: 62

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.925 AC: 74 AN: 80

European-Finnish (FIN) AF: 0.746 AC: 318 AN: 426

Middle Eastern (MID) AF: 0.774 AC: 1156 AN: 1494

European-Non Finnish (NFE) AF: 0.736 AC: 53 AN: 72

Other (OTH) AF: 0.637 AC: 107 AN: 168

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

African (AFR) AF: 0.367 AC: 15233 AN: 41452

American (AMR) AF: 0.787 AC: 12046 AN: 15298

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

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

South Asian (SAS) AF: 0.837 AC: 4040 AN: 4828

European-Finnish (FIN) AF: 0.751 AC: 7929 AN: 10560

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54470 AN: 67972

Other (OTH) AF: 0.719 AC: 1519 AN: 2112

Alfa AF: 0.596 Hom.: 5393

Bravo AF: 0.665

Asia WGS AF: 0.755 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.94
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: rs9068; hg19: chr2-178085137; COSMIC: COSV66820705; COSMIC: COSV66820705;