dbSNP rs9068: HNRNPA3:c.*1017G>A (chr2-177220409-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.940

Publications

12 publications found

Variant links:

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]

HNRNPA3 links:

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

NFE2L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA3	NM_194247.4 link	c.*1017G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000392524.7	NP_919223.1	P51991-1A0A384NL63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000392524.7 link	c.*1017G>A		3_prime_UTR_variant	Exon 11 of 11	5	NM_194247.4	ENSP00000376309.2		P51991-1

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102876

AN:

151954

Hom.:

37669

Cov.:

show subpopulations

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.:

AF XY:

0.766

AC XY:

902

AN XY:

1178

show subpopulations

African (AFR)

AF:

0.355

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.925

AC:

AN:

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:

AN:

Other (OTH)

AF:

0.637

AC:

107

AN:

168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.677

AC:

102896

AN:

152072

Hom.:

37680

Cov.:

AF XY:

0.679

AC XY:

50493

AN XY:

74360

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1440

2880

4320

5760

7200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.94

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over