14-21209535-T-C

Variant names:

• chr14-21209535-T-C
• rs7495
• NM_004500.4:c.*1688A>G

Variant summary

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

The NM_004500.4(HNRNPC):​c.*1688A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,064 control chromosomes in the GnomAD database, including 9,168 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 (9168 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HNRNPC NM_004500.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• 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=-0.89).
• 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.*1688A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000553300.6	NP_004491.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPC	ENST00000553300.6	c.*1688A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_004500.4	ENSP00000450544.1
HNRNPC	ENST00000336053.10	c.*1802A>G		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000338095.6

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52291 AN: 151946 Hom.: 9148 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.318

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.344 AC: 52344 AN: 152064 Hom.: 9168 Cov.: 32 AF XY: 0.347 AC XY: 25810 AN XY: 74342

African (AFR) AF: 0.337 AC: 13987 AN: 41478

American (AMR) AF: 0.391 AC: 5969 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1569 AN: 5184

South Asian (SAS) AF: 0.347 AC: 1673 AN: 4826

European-Finnish (FIN) AF: 0.357 AC: 3768 AN: 10546

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

European-Non Finnish (NFE) AF: 0.343 AC: 23307 AN: 67966

Other (OTH) AF: 0.315 AC: 666 AN: 2112

Alfa AF: 0.343 Hom.: 17544

Bravo AF: 0.344

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.59
DANN	Benign	0.56
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7495; hg19: chr14-21677694;