12-54281329-G-A

Position:

• chr12-54281329-G-A

Variant summary

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

The NM_031157.4(HNRNPA1):​c.16-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 959,644 control chromosomes in the GnomAD database, including 16,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2362 hom., cov: 32)
  • Exomes 𝑓: 0.17 (13943 hom.)
• Consequence: HNRNPA1 NM_031157.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.114

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-54281329-G-A is Benign according to our data. Variant chr12-54281329-G-A is described in ClinVar as [Benign]. Clinvar id is 1281374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPA1	NM_031157.4	c.16-57G>A		intron_variant		ENST00000340913.11	NP_112420.1
HNRNPA1	NM_002136.4	c.16-57G>A		intron_variant			NP_002127.1
HNRNPA1	NR_135167.2	n.98-57G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPA1	ENST00000340913.11	c.16-57G>A		intron_variant		1	NM_031157.4	ENSP00000341826.7

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24225 AN: 151884 Hom.: 2362 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0595

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.168 AC: 135545 AN: 807642 Hom.: 13943 Cov.: 11 AF XY: 0.167 AC XY: 71169 AN XY: 425712

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.159 AC: 24229 AN: 152002 Hom.: 2362 Cov.: 32 AF XY: 0.170 AC XY: 12606 AN XY: 74256

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.142

Alfa AF: 0.114 Hom.: 278

Bravo AF: 0.152

Asia WGS AF: 0.335 AC: 1162 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.55
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs2071391; hg19: chr12-54675113; COSMIC: COSV52938097; COSMIC: COSV52938097;