Variant 12-54284196-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.426

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:

(HGNC:):

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=-0.82).

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_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HNRNPA1	NM_031157.4 linkuse as main transcript	c.1064-62C>T	intron_variant	ENST00000340913.11
HNRNPA1	NM_002136.4 linkuse as main transcript	c.908-62C>T	intron_variant
HNRNPA1	NR_135167.2 linkuse as main transcript	n.990-62C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPA1	ENST00000340913.11 linkuse as main transcript	c.1064-62C>T		intron_variant		1	NM_031157.4		P09651-1
	ENST00000553061.1 linkuse as main transcript	n.545+7021C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

116054

AN:

152094

Hom.:

45758

Cov.:

show subpopulations

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.:

AF XY:

0.692

AC XY:

481631

AN XY:

695560

show subpopulations

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.:

AF XY:

0.771

AC XY:

57360

AN XY:

74404

show subpopulations

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

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

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