Variant 12-54281778-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_031157.4(HNRNPA1):c.133-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,606,530 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 16 hom. )

Consequence

HNRNPA1
NM_031157.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.929

Variant links:

Genes affected

HNRNPA1 (HGNC:5031): (heterogeneous nuclear ribonucleoprotein A1) This gene encodes a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs), which are RNA-binding proteins that associate with pre-mRNAs in the nucleus and influence pre-mRNA processing, as well as other aspects of mRNA metabolism and transport. The protein encoded by this gene is one of the most abundant core proteins of hnRNP complexes and plays a key role in the regulation of alternative splicing. Mutations in this gene have been observed in individuals with amyotrophic lateral sclerosis 20. Multiple alternatively spliced transcript variants have been found. There are numerous pseudogenes of this gene distributed throughout the genome. [provided by RefSeq, Feb 2016]

HNRNPA1 links:

HNRNPA1 (HGNC:):

HNRNPA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-54281778-A-G is Benign according to our data. Variant chr12-54281778-A-G is described in ClinVar as [Benign]. Clinvar id is 261941.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-54281778-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00289 (440/152284) while in subpopulation AMR AF= 0.00811 (124/15292). AF 95% confidence interval is 0.00695. There are 1 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
HNRNPA1	NM_031157.4 linkuse as main transcript	c.133-17A>G	intron_variant	ENST00000340913.11	NP_112420.1	P09651-1A0A024RAZ7
HNRNPA1	NM_002136.4 linkuse as main transcript	c.133-17A>G	intron_variant		NP_002127.1	P09651-2A0A024RB53
HNRNPA1	NR_135167.2 linkuse as main transcript	n.215-17A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPA1	ENST00000340913.11 linkuse as main transcript	c.133-17A>G		intron_variant		1	NM_031157.4	ENSP00000341826.7		P09651-1

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00388

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00262

AC:

638

AN:

243232

Hom.:

AF XY:

0.00260

AC XY:

344

AN XY:

132348

show subpopulations

Gnomad AFR exome

AF:

0.000784

Gnomad AMR exome

AF:

0.00479

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.00367

Gnomad OTH exome

AF:

0.00274

GnomAD4 exome

AF:

0.00413

AC:

6013

AN:

1454246

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

2867

AN XY:

723350

show subpopulations

Gnomad4 AFR exome

AF:

0.000667

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.00151

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00459

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152284

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

200

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00811

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00388

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00316

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over