1-244856718-T-G

Variant names:

• chr1-244856718-T-G
• rs75053711
• NM_031844.3:c.1743+10A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031844.3(HNRNPU):​c.1743+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,609,452 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (153 hom.)
• Consequence: HNRNPU NM_031844.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.641
• Publications: 4 publications found

Genes affected

HNRNPU (HGNC:5048): (heterogeneous nuclear ribonucleoprotein U) This gene encodes a member of a family of proteins that bind nucleic acids and function in the formation of ribonucleoprotein complexes in the nucleus with heterogeneous nuclear RNA (hnRNA). The encoded protein has affinity for both RNA and DNA, and binds scaffold-attached region (SAR) DNA. Mutations in this gene have been associated with epileptic encephalopathy, early infantile, 54. A pseudogene of this gene has been identified on chromosome 14. [provided by RefSeq, Jun 2017]

HNRNPU Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 54

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-244856718-T-G is Benign according to our data. Variant chr1-244856718-T-G is described in ClinVar as Benign. ClinVar VariationId is 414097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031844.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPU	NM_031844.3	MANE Select	c.1743+10A>C		intron	N/A	NP_114032.2
	HNRNPU	NM_004501.3		c.1686+10A>C		intron	N/A	NP_004492.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPU	ENST00000640218.2	TSL:1 MANE Select	c.1743+10A>C		intron	N/A	ENSP00000491215.1
	HNRNPU	ENST00000444376.7	TSL:1	c.1686+10A>C		intron	N/A	ENSP00000393151.2
	HNRNPU	ENST00000639628.2	TSL:1	c.915+10A>C		intron	N/A	ENSP00000491340.1

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 514 AN: 152232 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00728 AC: 1798 AN: 247130 AF XY: 0.00676

Gnomad AFR exome AF: 0.0000628

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.000813

Gnomad EAS exome AF: 0.0896

Gnomad FIN exome AF: 0.00339

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00261 AC: 3805 AN: 1457102 Hom.: 153 Cov.: 31 AF XY: 0.00259 AC XY: 1880 AN XY: 724676

African (AFR) AF: 0.000121 AC: 4 AN: 33042

American (AMR) AF: 0.0000459 AC: 2 AN: 43582

Ashkenazi Jewish (ASJ) AF: 0.000579 AC: 15 AN: 25916

East Asian (EAS) AF: 0.0792 AC: 3141 AN: 39660

South Asian (SAS) AF: 0.00183 AC: 156 AN: 85084

European-Finnish (FIN) AF: 0.00290 AC: 155 AN: 53362

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5742

European-Non Finnish (NFE) AF: 0.000141 AC: 157 AN: 1110554

Other (OTH) AF: 0.00286 AC: 172 AN: 60160

GnomAD4 genome AF: 0.00337 AC: 514 AN: 152350 Hom.: 23 Cov.: 32 AF XY: 0.00412 AC XY: 307 AN XY: 74500

African (AFR) AF: 0.0000962 AC: 4 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.0851 AC: 441 AN: 5182

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68038

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00241 Hom.: 6

Bravo AF: 0.00392

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 18, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Developmental and epileptic encephalopathy, 54 Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.54
PhyloP100		0.64
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: rs75053711; hg19: chr1-245020020; COSMIC: COSV51689144; COSMIC: COSV51689144;