12-54280451-A-G

Variant names:

• chr12-54280451-A-G
• rs3809162
• ENST00000546500:c.-357A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000546500(HNRNPA1):​c.-357A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 435,470 control chromosomes in the GnomAD database, including 51,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (22453 hom., cov: 33)
  • Exomes 𝑓: 0.44 (29260 hom.)
• Consequence: HNRNPA1 ENST00000546500 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.844

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]

ENSG00000258344 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-54280451-A-G is Benign according to our data. Variant chr12-54280451-A-G is described in ClinVar as [Benign]. Clinvar id is 1238025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA1	ENST00000546500	c.-357A>G		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000448617.1
ENSG00000258344	ENST00000553061.1	n.545+3276A>G		intron_variant	Intron 1 of 1	5
HNRNPA1	ENST00000677210.1	c.-357A>G		upstream_gene_variant				ENSP00000503610.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78657 AN: 152006 Hom.: 22406 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.441 AC: 124819 AN: 283346 Hom.: 29260 Cov.: 0 AF XY: 0.442 AC XY: 65701 AN XY: 148484

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.426

GnomAD4 genome AF: 0.518 AC: 78762 AN: 152124 Hom.: 22453 Cov.: 33 AF XY: 0.522 AC XY: 38804 AN XY: 74362

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.455

Alfa AF: 0.391 Hom.: 11413

Bravo AF: 0.527

Asia WGS AF: 0.580 AC: 2018 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs3809162; hg19: chr12-54674235;