1-23338018-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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

African (AFR) AF: 0.217 AC: 2566 AN: 11800

American (AMR) AF: 0.456 AC: 8319 AN: 18258

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 9820 AN: 13296

East Asian (EAS) AF: 0.559 AC: 16677 AN: 29822

South Asian (SAS) AF: 0.566 AC: 24215 AN: 42766

European-Finnish (FIN) AF: 0.746 AC: 21519 AN: 28828

Middle Eastern (MID) AF: 0.723 AC: 2415 AN: 3342

European-Non Finnish (NFE) AF: 0.732 AC: 196461 AN: 268294

Other (OTH) AF: 0.654 AC: 16600 AN: 25388

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

African (AFR) AF: 0.218 AC: 9045 AN: 41472

American (AMR) AF: 0.507 AC: 7749 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2639 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3056 AN: 5178

South Asian (SAS) AF: 0.551 AC: 2652 AN: 4816

European-Finnish (FIN) AF: 0.732 AC: 7742 AN: 10570

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.732 AC: 49797 AN: 68000

Other (OTH) AF: 0.587 AC: 1235 AN: 2104

Alfa AF: 0.685 Hom.: 50924

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
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV107393633; COSMIC: COSV107393633;