rs34734159

Positions:

• chr5-179616981-C-CAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001257293.2(HNRNPH1):​c.1118-24_1118-23insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,253,920 control chromosomes in the GnomAD database, including 72,214 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15534 hom., cov: 0)
  • Exomes 𝑓: 0.21 (56680 hom.)
• Consequence: HNRNPH1 NM_001257293.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

Genes affected

HNRNPH1 (HGNC:5041): (heterogeneous nuclear ribonucleoprotein H1) This gene encodes a member of a subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA. 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 may 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 RNA and is very similar to the family member HNRPF. This gene may be associated with hereditary lymphedema type I. Alternatively spliced transcript variants have been described [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPH1	NM_001257293.2	c.1118-24_1118-23insTT		intron_variant		ENST00000393432.9	NP_001244222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPH1	ENST00000393432.9	c.1118-24_1118-23insTT		intron_variant		1	NM_001257293.2	ENSP00000377082	P4

Frequencies

GnomAD3 genomes AF: 0.448 AC: 62169 AN: 138852 Hom.: 15533 Cov.: 0

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.412

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.421

GnomAD3 exomes AF: 0.230 AC: 30366 AN: 131792 Hom.: 7742 AF XY: 0.217 AC XY: 14754 AN XY: 67878

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.115

Gnomad SAS exome AF: 0.0914

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.322

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.206 AC: 229602 AN: 1114964 Hom.: 56680 Cov.: 34 AF XY: 0.215 AC XY: 121789 AN XY: 565632

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.448 AC: 62191 AN: 138956 Hom.: 15534 Cov.: 0 AF XY: 0.441 AC XY: 29641 AN XY: 67278

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.416

Alfa AF: 0.484 Hom.: 2134

Asia WGS AF: 0.192 AC: 617 AN: 3206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34734159; hg19: chr5-179043982;