12-54284196-C-T

Variant names:

• chr12-54284196-C-T
• rs7967622
• NM_031157.4:c.1064-62C>T

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.1064-62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,545,004 control chromosomes in the GnomAD database, including 384,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (45827 hom., cov: 33)
  • Exomes 𝑓: 0.69 (338255 hom.)
• Consequence: HNRNPA1 NM_031157.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.426

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 12-54284196-C-T is Benign according to our data. Variant chr12-54284196-C-T is described in ClinVar as [Benign]. Clinvar id is 1226405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA1	NM_031157.4	c.1064-62C>T		intron_variant	Intron 9 of 10	ENST00000340913.11	NP_112420.1
HNRNPA1	NM_002136.4	c.908-62C>T		intron_variant	Intron 8 of 9		NP_002127.1
HNRNPA1	NR_135167.2	n.990-62C>T		intron_variant	Intron 8 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA1	ENST00000340913.11	c.1064-62C>T		intron_variant	Intron 9 of 10	1	NM_031157.4	ENSP00000341826.7

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116054 AN: 152094 Hom.: 45758 Cov.: 33

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.690 AC: 961060 AN: 1392792 Hom.: 338255 Cov.: 21 AF XY: 0.692 AC XY: 481631 AN XY: 695560

Gnomad4 AFR exome AF: 0.950

Gnomad4 AMR exome AF: 0.823

Gnomad4 ASJ exome AF: 0.597

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.709

GnomAD4 genome AF: 0.763 AC: 116185 AN: 152212 Hom.: 45827 Cov.: 33 AF XY: 0.771 AC XY: 57360 AN XY: 74404

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.731

Alfa AF: 0.656 Hom.: 33748

Bravo AF: 0.771

Asia WGS AF: 0.944 AC: 3280 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

- -

May 12, 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	1.5
DANN	Benign	0.32

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: rs7967622; hg19: chr12-54677980;