rs2241715

Variant names:

• chr19-41350981-A-C
• rs2241715
• ENST00000539627.5:c.-251A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-41350981-A-C
• chr19-41350981-A-G
• chr19-41350981-A-T

Variant summary

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

The ENST00000539627.5(TMEM91):​c.-251A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,260 control chromosomes in the GnomAD database, including 34,737 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 0.67 (34659 hom., cov: 30)
  • Exomes 𝑓: 0.61 (78 hom.)
• Consequence: TMEM91 ENST00000539627.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 59 publications found

Genes affected

TMEM91 (HGNC:32393): (transmembrane protein 91) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• inflammatory bowel disease, immunodeficiency, and encephalopathy

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000255730 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFB1	NM_000660.7	c.355+1709T>G		intron_variant	Intron 1 of 6	ENST00000221930.6	NP_000651.3
TGFB1	XM_011527242.3	c.355+1709T>G		intron_variant	Intron 1 of 6		XP_011525544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB1	ENST00000221930.6	c.355+1709T>G		intron_variant	Intron 1 of 6	1	NM_000660.7	ENSP00000221930.4

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101794 AN: 151702 Hom.: 34643 Cov.: 30

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.611 AC: 270 AN: 442 Hom.: 78 Cov.: 0 AF XY: 0.615 AC XY: 161 AN XY: 262

African (AFR) AF: 0.500 AC: 6 AN: 12

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 2 AN: 8

East Asian (EAS) AF: 0.462 AC: 12 AN: 26

South Asian (SAS) AF: 0.500 AC: 5 AN: 10

European-Finnish (FIN) AF: 0.635 AC: 47 AN: 74

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.645 AC: 182 AN: 282

Other (OTH) AF: 0.538 AC: 14 AN: 26

GnomAD4 genome AF: 0.671 AC: 101855 AN: 151818 Hom.: 34659 Cov.: 30 AF XY: 0.668 AC XY: 49528 AN XY: 74176

African (AFR) AF: 0.711 AC: 29409 AN: 41342

American (AMR) AF: 0.564 AC: 8605 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2311 AN: 5154

South Asian (SAS) AF: 0.611 AC: 2945 AN: 4818

European-Finnish (FIN) AF: 0.743 AC: 7847 AN: 10556

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46671 AN: 67924

Other (OTH) AF: 0.626 AC: 1317 AN: 2104

Alfa AF: 0.669 Hom.: 48055

Bravo AF: 0.658

Asia WGS AF: 0.537 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.46
PhyloP100		-2.5
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95
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: rs2241715; hg19: chr19-41856886;