1-23338018-T-C

Variant names:

• chr1-23338018-T-C
• rs11586100
• NM_005826.5:c.277-157A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005826.5(HNRNPR):​c.277-157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HNRNPR NM_005826.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 11 publications found

Genes affected

HNRNPR (HGNC:5047): (heterogeneous nuclear ribonucleoprotein R) This gene encodes an RNA-binding protein that is a member of the spliceosome C complex, which functions in pre-mRNA processing and transport. The encoded protein also promotes transcription at the c-fos gene. Alternative splicing results in multiple transcript variants. There are pseudogenes for this gene on chromosomes 4, 11, and 10. [provided by RefSeq, Jul 2014]

HNRNPR Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPR	NM_005826.5	c.277-157A>G		intron_variant	Intron 3 of 10	ENST00000302271.11	NP_005817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPR	ENST00000302271.11	c.277-157A>G		intron_variant	Intron 3 of 10	1	NM_005826.5	ENSP00000304405.6
HNRNPR	ENST00000374616.7	c.277-157A>G		intron_variant	Intron 3 of 10	1		ENSP00000363745.3
HNRNPR	ENST00000478691.5	c.-27-157A>G		intron_variant	Intron 2 of 9	1		ENSP00000474437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 442692 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 235558

African (AFR) AF: 0.00 AC: 0 AN: 11828

American (AMR) AF: 0.00 AC: 0 AN: 18310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13326

East Asian (EAS) AF: 0.00 AC: 0 AN: 29890

South Asian (SAS) AF: 0.00 AC: 0 AN: 42852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 268784

Other (OTH) AF: 0.00 AC: 0 AN: 25454

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.5
DANN	Benign	0.47
PhyloP100		0.18

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: rs11586100; hg19: chr1-23664511;