Genetic Variant NM_004500.4:c.317+87T>G (chr14-21230910-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004500.4(HNRNPC):c.317+87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,429,018 control chromosomes in the GnomAD database, including 45,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4035 hom., cov: 31)

Exomes 𝑓: 0.25 ( 41382 hom. )

Consequence

HNRNPC
NM_004500.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

11 publications found

Variant links:

Genes affected

HNRNPC (HGNC:5035): (heterogeneous nuclear ribonucleoprotein C) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene can act as a tetramer and is involved in the assembly of 40S hnRNP particles. Multiple transcript variants encoding at least two different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

HNRNPC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPC	NM_004500.4 link	c.317+87T>G		intron_variant	Intron 4 of 8	ENST00000553300.6	NP_004491.2	P07910-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPC	ENST00000553300.6 link	c.317+87T>G		intron_variant	Intron 4 of 8	1	NM_004500.4	ENSP00000450544.1		P07910-2

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32443

AN:

151948

Hom.:

4028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0962

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.209

GnomAD2 exomes

AF:

0.263

AC:

62230

AN:

236738

AF XY:

0.262

show subpopulations

Gnomad AFR exome

AF:

0.0970

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.249

AC:

318170

AN:

1276952

Hom.:

41382

Cov.:

AF XY:

0.250

AC XY:

160540

AN XY:

642784

show subpopulations

African (AFR)

AF:

0.0910

AC:

2672

AN:

29368

American (AMR)

AF:

0.375

AC:

15204

AN:

40538

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

5614

AN:

24048

East Asian (EAS)

AF:

0.283

AC:

10938

AN:

38662

South Asian (SAS)

AF:

0.280

AC:

22157

AN:

79084

European-Finnish (FIN)

AF:

0.223

AC:

11749

AN:

52728

Middle Eastern (MID)

AF:

0.247

AC:

1313

AN:

5324

European-Non Finnish (NFE)

AF:

0.248

AC:

235917

AN:

953116

Other (OTH)

AF:

0.233

AC:

12606

AN:

54084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11545

23090

34635

46180

57725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7726

15452

23178

30904

38630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.213

AC:

32456

AN:

152066

Hom.:

4035

Cov.:

AF XY:

0.217

AC XY:

16138

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0962

AC:

3994

AN:

41516

American (AMR)

AF:

0.317

AC:

4842

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

822

AN:

3466

East Asian (EAS)

AF:

0.300

AC:

1547

AN:

5158

South Asian (SAS)

AF:

0.289

AC:

1392

AN:

4820

European-Finnish (FIN)

AF:

0.214

AC:

2259

AN:

10580

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16838

AN:

67938

Other (OTH)

AF:

0.209

AC:

440

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1272

2545

3817

5090

6362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.242

Hom.:

2742

Bravo

AF:

0.216

Asia WGS

AF:

0.293

AC:

1019

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

2.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over