rs17092523

Variant names:

• chr14-21250759-C-T
• rs17092523
• NM_004500.4:c.-37+12552G>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.-37+12552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,170 control chromosomes in the GnomAD database, including 1,711 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 0.14 (1711 hom., cov: 31)
• Consequence: HNRNPC NM_004500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPC	NM_004500.4	c.-37+12552G>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.-37+12552G>A		intron_variant	Intron 2 of 8	1	NM_004500.4	ENSP00000450544.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21310 AN: 152052 Hom.: 1704 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.140 AC: 21332 AN: 152170 Hom.: 1711 Cov.: 31 AF XY: 0.143 AC XY: 10646 AN XY: 74376

African (AFR) AF: 0.138 AC: 5745 AN: 41506

American (AMR) AF: 0.228 AC: 3491 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.0853 AC: 442 AN: 5184

South Asian (SAS) AF: 0.113 AC: 547 AN: 4820

European-Finnish (FIN) AF: 0.161 AC: 1702 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8728 AN: 68006

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.141 Hom.: 594

Bravo AF: 0.146

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.79
PhyloP100		0.33
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: rs17092523; hg19: chr14-21718918;