rs17197037

Variant names:

• chr14-21257495-G-A
• rs17197037
• NM_004500.4:c.-37+5816C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004500.4(HNRNPC):​c.-37+5816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,686 control chromosomes in the GnomAD database, including 10,597 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 0.36 (10597 hom., cov: 30)
• Consequence: HNRNPC NM_004500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 23 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004500.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPC	NM_004500.4	MANE Select	c.-37+5816C>T		intron	N/A	NP_004491.2
	HNRNPC	NM_001077442.2		c.-37+11803C>T		intron	N/A	NP_001070910.1
	HNRNPC	NM_031314.3		c.-37+5816C>T		intron	N/A	NP_112604.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPC	ENST00000553300.6	TSL:1 MANE Select	c.-37+5816C>T		intron	N/A	ENSP00000450544.1
	HNRNPC	ENST00000554455.5	TSL:1	c.-37+5816C>T		intron	N/A	ENSP00000451291.1
	HNRNPC	ENST00000557201.5	TSL:1	c.-37+11803C>T		intron	N/A	ENSP00000452276.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55102 AN: 151566 Hom.: 10595 Cov.: 30

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.414

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55109 AN: 151686 Hom.: 10597 Cov.: 30 AF XY: 0.361 AC XY: 26709 AN XY: 74086

African (AFR) AF: 0.274 AC: 11334 AN: 41336

American (AMR) AF: 0.344 AC: 5256 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1811 AN: 3466

East Asian (EAS) AF: 0.688 AC: 3555 AN: 5166

South Asian (SAS) AF: 0.391 AC: 1875 AN: 4794

European-Finnish (FIN) AF: 0.323 AC: 3376 AN: 10436

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26506 AN: 67922

Other (OTH) AF: 0.418 AC: 877 AN: 2100

Alfa AF: 0.391 Hom.: 46797

Bravo AF: 0.363

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.51
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17197037; hg19: chr14-21725654;