1-23338018-T-G

Variant names:

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

Variant summary

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

The NM_005826.5(HNRNPR):​c.277-157A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 593,882 control chromosomes in the GnomAD database, including 131,802 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 0.56 (27499 hom., cov: 32)
  • Exomes 𝑓: 0.68 (104303 hom.)
• Consequence: HNRNPR NM_005826.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84857 AN: 151970 Hom.: 27501 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.592

GnomAD4 exome AF: 0.676 AC: 298592 AN: 441794 Hom.: 104303 Cov.: 5 AF XY: 0.674 AC XY: 158494 AN XY: 235102

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.739

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.746

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.558 AC: 84861 AN: 152088 Hom.: 27499 Cov.: 32 AF XY: 0.555 AC XY: 41271 AN XY: 74330

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.587

Alfa AF: 0.704 Hom.: 42605

Bravo AF: 0.525

Asia WGS AF: 0.505 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.51

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: rs11586100; hg19: chr1-23664511;