16-31473920-C-T

Variant names:

• chr16-31473920-C-T
• rs140328458
• NM_001042454.3:c.268C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001042454.3(TGFB1I1):​c.268C>T​(p.Leu90Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L90V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TGFB1I1 NM_001042454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.43
• Publications: 0 publications found

Genes affected

TGFB1I1 (HGNC:11767): (transforming growth factor beta 1 induced transcript 1) This gene encodes a coactivator of the androgen receptor, a transcription factor which is activated by androgen and has a key role in male sexual differentiation. The encoded protein is thought to regulate androgen receptor activity and may have a role to play in the treatment of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042454.3. 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
	TGFB1I1	NM_001042454.3	MANE Select	c.268C>T	p.Leu90Phe	missense	Exon 4 of 11	NP_001035919.1	O43294-1
	TGFB1I1	NM_001164719.1		c.217C>T	p.Leu73Phe	missense	Exon 4 of 11	NP_001158191.1	O43294-2
	TGFB1I1	NM_015927.5		c.217C>T	p.Leu73Phe	missense	Exon 4 of 11	NP_057011.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB1I1	ENST00000394863.8	TSL:1 MANE Select	c.268C>T	p.Leu90Phe	missense	Exon 4 of 11	ENSP00000378332.3	O43294-1
	TGFB1I1	ENST00000361773.7	TSL:1	c.217C>T	p.Leu73Phe	missense	Exon 4 of 11	ENSP00000355117.3	O43294-2
	TGFB1I1	ENST00000394858.6	TSL:1	c.217C>T	p.Leu73Phe	missense	Exon 4 of 11	ENSP00000378327.2	O43294-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251310 AF XY: 0.00000736

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.015	D
Polyphen		0.89	P
Vest4		0.42
MutPred		0.44		Loss of disorder (P = 0.1616)
MVP		0.70
MPC		0.30
ClinPred		0.99	D
GERP RS		4.9
PromoterAI		0.0075	Neutral
Varity_R		0.38
gMVP		0.60

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: rs140328458; hg19: chr16-31485241;