10-43385627-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098204.2(HNRNPF):c.*1010T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,132 control chromosomes in the GnomAD database, including 21,135 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 0.50 (21135 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: HNRNPF NM_001098204.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

Genes affected

HNRNPF (HGNC:5039): (heterogeneous nuclear ribonucleoprotein F) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and regulate alternative splicing, polyadenylation, 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 has three repeats of quasi-RRM domains that bind to RNAs which have guanosine-rich sequences. This protein is very similar to the family member hnRPH. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPF	NM_001098204.2	c.*1010T>C		3_prime_UTR_variant	4/4	ENST00000682386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPF	ENST00000682386.1	c.*1010T>C		3_prime_UTR_variant	4/4		NM_001098204.2	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75821 AN: 152014 Hom.: 21090 Cov.: 33

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.499 AC: 75914 AN: 152132 Hom.: 21135 Cov.: 33 AF XY: 0.495 AC XY: 36786 AN XY: 74376

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.458

Alfa AF: 0.446 Hom.: 5303

Bravo AF: 0.506

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.1
Dann	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs7905676; hg19: chr10-43881075;