5-179616981-C-CAA

Variant names:

• chr5-179616981-C-CAA
• rs34734159
• NM_001257293.2:c.1118-25_1118-24dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001257293.2(HNRNPH1):​c.1118-25_1118-24dupTT 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
• Publications: 3 publications found

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]

HNRNPH1 Gene-Disease associations (from GenCC):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LOC128966623 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257293.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPH1	NM_001257293.2	MANE Select	c.1118-25_1118-24dupTT		intron	N/A	NP_001244222.1	A0A384MEJ3
	HNRNPH1	NM_001364225.2		c.1118-25_1118-24dupTT		intron	N/A	NP_001351154.1	G8JLB6
	HNRNPH1	NM_001364226.2		c.1118-25_1118-24dupTT		intron	N/A	NP_001351155.1	G8JLB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPH1	ENST00000393432.9	TSL:1 MANE Select	c.1118-25_1118-24dupTT		intron	N/A	ENSP00000377082.4	P31943
	HNRNPH1	ENST00000442819.6	TSL:1	c.1118-25_1118-24dupTT		intron	N/A	ENSP00000397797.2	P31943
	HNRNPH1	ENST00000329433.11	TSL:2	c.1118-25_1118-24dupTT		intron	N/A	ENSP00000327539.6	G8JLB6

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

GnomAD2 exomes AF: 0.230 AC: 30366 AN: 131792 AF XY: 0.217

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 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

African (AFR) AF: 0.168 AC: 4882 AN: 29062

American (AMR) AF: 0.136 AC: 5792 AN: 42468

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5468 AN: 23870

East Asian (EAS) AF: 0.185 AC: 7209 AN: 39038

South Asian (SAS) AF: 0.199 AC: 15894 AN: 80032

European-Finnish (FIN) AF: 0.467 AC: 24071 AN: 51578

Middle Eastern (MID) AF: 0.290 AC: 1525 AN: 5258

European-Non Finnish (NFE) AF: 0.192 AC: 152382 AN: 793554

Other (OTH) AF: 0.247 AC: 12379 AN: 50104

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

African (AFR) AF: 0.373 AC: 13844 AN: 37076

American (AMR) AF: 0.344 AC: 4805 AN: 13984

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1269 AN: 3272

East Asian (EAS) AF: 0.196 AC: 938 AN: 4774

South Asian (SAS) AF: 0.303 AC: 1302 AN: 4300

European-Finnish (FIN) AF: 0.544 AC: 4932 AN: 9068

Middle Eastern (MID) AF: 0.402 AC: 106 AN: 264

European-Non Finnish (NFE) AF: 0.531 AC: 33686 AN: 63416

Other (OTH) AF: 0.416 AC: 802 AN: 1928

Alfa AF: 0.484 Hom.: 2134

Asia WGS AF: 0.192 AC: 617 AN: 3206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
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: rs34734159; hg19: chr5-179043982;