rs11881940

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-41302527-A-C
• chr19-41302527-A-G
• chr19-41302527-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007040.6(HNRNPUL1):​c.1688-138A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000307 in 977,624 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000031 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A	NP_008971.2
	HNRNPUL1	NM_001439168.1		c.1688-138A>C		intron	N/A	NP_001426097.1
	HNRNPUL1	NM_001439167.1		c.1688-138A>C		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>C		intron	N/A	ENSP00000375863.2	Q9BUJ2-1
	HNRNPUL1	ENST00000602130.5	TSL:1	c.1688-138A>C		intron	N/A	ENSP00000470687.1	Q9BUJ2-2
	HNRNPUL1	ENST00000352456.7	TSL:1	c.1388-138A>C		intron	N/A	ENSP00000340857.3	A0A0A0MRA5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000494 AC: 1 AN: 202316 AF XY: 0.00000904

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000113

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000307 AC: 3 AN: 977624 Hom.: 0 Cov.: 13 AF XY: 0.00000595 AC XY: 3 AN XY: 504136

African (AFR) AF: 0.00 AC: 0 AN: 24098

American (AMR) AF: 0.00 AC: 0 AN: 40024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22854

East Asian (EAS) AF: 0.00 AC: 0 AN: 37084

South Asian (SAS) AF: 0.00 AC: 0 AN: 74210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4882

European-Non Finnish (NFE) AF: 0.00000291 AC: 2 AN: 686426

Other (OTH) AF: 0.0000225 AC: 1 AN: 44492

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.25
PhyloP100		-1.2

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;