16-31473527-C-T

Variant names:

• chr16-31473527-C-T
• rs761049909
• NM_001042454.3:c.100C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001042454.3(TGFB1I1):​c.100C>T​(p.Pro34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TGFB1I1 NM_001042454.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037683785).
• BP6: Variant 16-31473527-C-T is Benign according to our data. Variant chr16-31473527-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3806395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 11 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.100C>T	p.Pro34Ser	missense	Exon 2 of 11	NP_001035919.1	O43294-1
	TGFB1I1	NM_001164719.1		c.49C>T	p.Pro17Ser	missense	Exon 2 of 11	NP_001158191.1	O43294-2
	TGFB1I1	NM_015927.5		c.49C>T	p.Pro17Ser	missense	Exon 2 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.100C>T	p.Pro34Ser	missense	Exon 2 of 11	ENSP00000378332.3	O43294-1
	TGFB1I1	ENST00000361773.7	TSL:1	c.49C>T	p.Pro17Ser	missense	Exon 2 of 11	ENSP00000355117.3	O43294-2
	TGFB1I1	ENST00000394858.6	TSL:1	c.49C>T	p.Pro17Ser	missense	Exon 2 of 11	ENSP00000378327.2	O43294-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250546 AF XY: 0.00000737

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461552 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727102

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53112

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

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111988

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.29
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.80	N
PhyloP100		0.24
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.048
Sift	Benign	0.35	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.16
MVP		0.13
MPC		0.049
ClinPred		0.056	T
GERP RS		1.0
PromoterAI		-0.015	Neutral
Varity_R		0.024
gMVP		0.26
Mutation Taster		=93/7	polymorphism

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: rs761049909; hg19: chr16-31484848; COSMIC: COSV62359041; COSMIC: COSV62359041;