rs6675421

Variant names:

• chr1-244864047-C-T
• rs6675421
• NM_031844.3:c.261G>A
• HNRNPU p.Glu87Glu

Your query was ambiguous. Multiple possible variants found:

• chr1-244864047-C-T
• chr1-244864047-C-A
• chr1-244864047-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_031844.3(HNRNPU):​c.261G>A​(p.Glu87Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,608,226 control chromosomes in the GnomAD database, including 50,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6618 hom., cov: 33)
  • Exomes 𝑓: 0.24 (43738 hom.)
• Consequence: HNRNPU NM_031844.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.468
• Publications: 17 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ENSG00000273175 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 1-244864047-C-T is Benign according to our data. Variant chr1-244864047-C-T is described in ClinVar as Benign. ClinVar VariationId is 586025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.468 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPU	NM_031844.3	MANE Select	c.261G>A	p.Glu87Glu	synonymous	Exon 1 of 14	NP_114032.2	Q00839-1
	HNRNPU	NM_004501.3		c.261G>A	p.Glu87Glu	synonymous	Exon 1 of 14	NP_004492.2	Q00839-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPU	ENST00000640218.2	TSL:1 MANE Select	c.261G>A	p.Glu87Glu	synonymous	Exon 1 of 14	ENSP00000491215.1	Q00839-1
	HNRNPU	ENST00000444376.7	TSL:1	c.261G>A	p.Glu87Glu	synonymous	Exon 1 of 14	ENSP00000393151.2	Q00839-2
	HNRNPU	ENST00000919769.1		c.261G>A	p.Glu87Glu	synonymous	Exon 1 of 15	ENSP00000589828.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43049 AN: 151940 Hom.: 6601 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.271 AC: 63556 AN: 234182 AF XY: 0.261

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.431

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.183

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.239 AC: 348360 AN: 1456170 Hom.: 43738 Cov.: 37 AF XY: 0.237 AC XY: 171824 AN XY: 724006

African (AFR) AF: 0.376 AC: 12541 AN: 33356

American (AMR) AF: 0.422 AC: 18584 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6243 AN: 26008

East Asian (EAS) AF: 0.140 AC: 5519 AN: 39460

South Asian (SAS) AF: 0.223 AC: 19165 AN: 85796

European-Finnish (FIN) AF: 0.338 AC: 17587 AN: 52100

Middle Eastern (MID) AF: 0.214 AC: 1230 AN: 5758

European-Non Finnish (NFE) AF: 0.228 AC: 252979 AN: 1109526

Other (OTH) AF: 0.241 AC: 14512 AN: 60168

GnomAD4 genome AF: 0.283 AC: 43090 AN: 152056 Hom.: 6618 Cov.: 33 AF XY: 0.287 AC XY: 21342 AN XY: 74292

African (AFR) AF: 0.370 AC: 15362 AN: 41484

American (AMR) AF: 0.347 AC: 5313 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3470

East Asian (EAS) AF: 0.175 AC: 900 AN: 5146

South Asian (SAS) AF: 0.201 AC: 966 AN: 4814

European-Finnish (FIN) AF: 0.351 AC: 3714 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15215 AN: 67950

Other (OTH) AF: 0.259 AC: 548 AN: 2116

Alfa AF: 0.240 Hom.: 1329

Bravo AF: 0.290

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Developmental and epileptic encephalopathy, 54 (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		-0.47
PromoterAI		-0.11	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6675421;

hg19: chr1-245027349;

COSMIC: COSV51690210;

COSMIC: COSV51690210;