rs4982436

Variant names:

• chr14-21248576-C-T
• rs4982436
• NM_004500.4:c.-36-14347G>A

Variant summary

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

The NM_004500.4(HNRNPC):​c.-36-14347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,952 control chromosomes in the GnomAD database, including 9,125 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 0.34 (9125 hom., cov: 31)
• Consequence: HNRNPC NM_004500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPC	NM_004500.4	c.-36-14347G>A		intron_variant	Intron 2 of 8	ENST00000553300.6	NP_004491.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPC	ENST00000553300.6	c.-36-14347G>A		intron_variant	Intron 2 of 8	1	NM_004500.4	ENSP00000450544.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52176 AN: 151832 Hom.: 9104 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.344 AC: 52233 AN: 151952 Hom.: 9125 Cov.: 31 AF XY: 0.347 AC XY: 25745 AN XY: 74256

African (AFR) AF: 0.337 AC: 13957 AN: 41426

American (AMR) AF: 0.391 AC: 5966 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1560 AN: 5180

South Asian (SAS) AF: 0.344 AC: 1657 AN: 4820

European-Finnish (FIN) AF: 0.359 AC: 3775 AN: 10528

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23249 AN: 67946

Other (OTH) AF: 0.316 AC: 665 AN: 2106

Alfa AF: 0.349 Hom.: 1205

Bravo AF: 0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.32
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4982436; hg19: chr14-21716735;