19-41302527-A-T

Variant names:

• chr19-41302527-A-T
• rs11881940
• NM_007040.6:c.1688-138A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007040.6(HNRNPUL1):​c.1688-138A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,128,630 control chromosomes in the GnomAD database, including 13,417 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 0.14 (1667 hom., cov: 31)
  • Exomes 𝑓: 0.15 (11750 hom.)
• Consequence: HNRNPUL1 NM_007040.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 8 publications found

Genes affected

HNRNPUL1 (HGNC:17011): (heterogeneous nuclear ribonucleoprotein U like 1) This gene encodes a nuclear RNA-binding protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. This protein binds specifically to adenovirus early-1B-55kDa oncoprotein. It may play an important role in nucleocytoplasmic RNA transport, and its function is modulated by early-1B-55kDa in adenovirus-infected cells. [provided by RefSeq, Mar 2016]

TGFB1 (HGNC:11766): (transforming growth factor beta 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]

TGFB1 Gene-Disease associations (from GenCC):

• Camurati-Engelmann disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics, PanelApp Australia
• inflammatory bowel disease, immunodeficiency, and encephalopathy

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007040.6. 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
	HNRNPUL1	NM_007040.6	MANE Select	c.1688-138A>T		intron	N/A	NP_008971.2
	HNRNPUL1	NM_001439168.1		c.1688-138A>T		intron	N/A	NP_001426097.1
	HNRNPUL1	NM_001439167.1		c.1688-138A>T		intron	N/A	NP_001426096.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPUL1	ENST00000392006.8	TSL:1 MANE Select	c.1688-138A>T		intron	N/A	ENSP00000375863.2	Q9BUJ2-1
	HNRNPUL1	ENST00000602130.5	TSL:1	c.1688-138A>T		intron	N/A	ENSP00000470687.1	Q9BUJ2-2
	HNRNPUL1	ENST00000352456.7	TSL:1	c.1388-138A>T		intron	N/A	ENSP00000340857.3	A0A0A0MRA5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20955 AN: 151852 Hom.: 1671 Cov.: 31

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.158

GnomAD2 exomes AF: 0.142 AC: 28758 AN: 202316 AF XY: 0.140

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.150 AC: 146777 AN: 976660 Hom.: 11750 Cov.: 13 AF XY: 0.148 AC XY: 74553 AN XY: 503684

African (AFR) AF: 0.0805 AC: 1940 AN: 24090

American (AMR) AF: 0.105 AC: 4214 AN: 40016

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3519 AN: 22842

East Asian (EAS) AF: 0.224 AC: 8318 AN: 37064

South Asian (SAS) AF: 0.0792 AC: 5875 AN: 74186

European-Finnish (FIN) AF: 0.151 AC: 6574 AN: 43520

Middle Eastern (MID) AF: 0.202 AC: 988 AN: 4880

European-Non Finnish (NFE) AF: 0.158 AC: 108155 AN: 685596

Other (OTH) AF: 0.162 AC: 7194 AN: 44466

GnomAD4 genome AF: 0.138 AC: 20945 AN: 151970 Hom.: 1667 Cov.: 31 AF XY: 0.135 AC XY: 10060 AN XY: 74264

African (AFR) AF: 0.0830 AC: 3443 AN: 41488

American (AMR) AF: 0.130 AC: 1992 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1412 AN: 5142

South Asian (SAS) AF: 0.0831 AC: 400 AN: 4812

European-Finnish (FIN) AF: 0.141 AC: 1484 AN: 10554

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10847 AN: 67912

Other (OTH) AF: 0.157 AC: 331 AN: 2106

Alfa AF: 0.105 Hom.: 205

Bravo AF: 0.139

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.37
PhyloP100		-1.2
Mutation Taster		=97/2	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: rs11881940; hg19: chr19-41808432; COSMIC: COSV54559943; COSMIC: COSV54559943;